Blood & Cancer

The official podcast feed of MDedge Hematology-Oncology, part of the Medscape Professional Network. On Thursdays, Dr. David Henry interviews key opinion leaders and rising stars in hematology and oncology. The information in this podcast is provided for informational and educational purposes only.

Biosimilars with Dr. Gary Lyman 05/27/2021

Biosimilars with Dr. Gary Lyman Existing biosimilars are safe, effective alternatives to their reference biologics, and are increasingly being incorporated into oncology treatment guidelines. Technological advances that have emerged in the years since biologic agents entered the market allow for the careful assessment of “critical clinical attributes” of biosimilar agents. This helps ensure the safety and efficacy of biosimilars, as well as their structural, functional, and behavioral similarities to the original reference biologics, according to , professor and senior lead, health care quality and policy at the Hutchinson Institute for Cancer Outcomes Research at Fred Hutchinson Cancer Research Center, Seattle. Biosimilars are increasingly being included as acceptable alternatives in treatment guidelines, and in this episode Dr. Lyman discussed the reasons why they are considered safe and effective, how they can add value for oncology patients, and the need for ongoing diligence in monitoring their effects. Biosimilars in oncology – key points: The developers of biosimilar agents must prove biosimilarity to the reference agent, and generally go through “many of the same, if not all, preclinical steps.” Regulatory requirements are sufficient to ensure there are no clinically meaningful differences in the safety, purity, strength, and efficacy of biosimilars. Unlike the originator biologics, biosimilars aren’t typically required to complete multiple costly phase 3 clinical studies that drive up drug costs. This has the potential to rein in drug prices for biologics, which have revolutionized oncology and many other fields – but at a significant price. There has been some progress with respect to biologic cost reductions in the wake of biosimilar approvals, but the cost effects of biosimilars for newer reference agents will take time to emerge. Further prolonging the cost-reducing effects of biosimilar availability is the fact that early biosimilars were mainly used for supportive care whereas newer biosimilars are more often used for curative intent, which may lead to slower uptake due to hesitancy among clinicians and patients. The European Medicines Agency (EMA) is about a decade ahead of the United States when it comes to approvals and acceptance of biosimilars. Of note, no approved biosimilar has been removed from the market due to concerns about safety and efficacy. This is “a huge testament to the durability of biosimilars and the strength of the regulatory process,” Dr. Lyman said, noting that the EMA and FDA have similar processes when it comes to such approvals. “Drift,” the inevitable changes over time in an agent’s characteristics, can lead to changes in safety and efficacy. This means that diligence in monitoring effects and outcomes with both biologics and biosimilars is essential. Any concerns should be reported immediately and investigated. Show notes written by Sharon Worcester, MA, a reporter for MDedge and Medscape. Disclosures Dr. Henry has no relevant disclosures. Dr. Lyman disclosed relationships with Amgen, Jazz Pharmaceuticals, Partners Therapeutics, Sandoz, Seattle Genetics, Bristol Myers Squibb, BeyondSpring, Samsung, G1 Therapeutics, and Merck. * * * For more MDedge Podcasts, go to Email the show: Interact with us on Twitter: David Henry on Twitter: /episode/index/show/jcsopodcast/id/19161224

Advanced bladder cancer: Dr. Arjun Balar talks treatment strategies in a changing field 05/20/2021

Advanced bladder cancer: Dr. Arjun Balar talks treatment strategies in a changing field Systemic treatment for advanced urothelial cancer is quickly evolving. On this week’s podcast, , MD, director of the genitourinary medical oncology program at New York University discusses his approach amid changing times with guest host Alan Lyss, MD, a community-based medical oncologist and clinical researcher in the St. Louis area before his recent retirement. Chemotherapy or immunotherapy first line? With the negative phase 3 results for chemotherapy in combination with either pembrolizumab or atezolizumab, “if I use immunotherapy, I use it alone,” Dr. Balar said. Patients who need “a response right away” for aggressive disease get chemotherapy. In general, first-line chemotherapy “probably is the better route for a lot of people,” he said. There is a role for immunotherapy in the first line when chemotherapy can’t be tolerated because of age or other reasons, and in the second line, immunotherapy is standard of care. PD-1/PD-LI expression is too inconsistent to help guide the decision. It’s based instead on clinical judgement, given patient and disease characteristics. Antibody-drug conjugates The class includes and , both approved for third-line treatment after chemo and immunotherapy. Essentially, they are homing molecules targeting cancer-specific antigens coupled with a potent cytotoxic payload. They have strong potential in combination with immunotherapy. “I think, in the next 3-5 years, we're going to find ADCs plus immunotherapy become the new standard of care,” Dr. Balar said. New enfortumab vedotin show activity in the second line among medically frail patients ineligible for chemotherapy who were treated instead with immunotherapy for metastatic disease. “This drug can potentially rescue those patients as an option after immunotherapy,” said Dr. Balar, an enfortumab vedotin investigator. Next-generation sequencing There’s no role yet for sequencing in the first line, but it’s necessary in later lines to check eligibility for drugs aimed at specific mutations, such as the tyrosine kinase inhibitor erdafitinib for patients with susceptible FGFR3 or FGFR2 genetic alterations. Assays are available commercially from and other companies. Results can take up to 6 weeks, so “I do it early on. I know that information is potentially going to be useful in making treatment decisions,” Dr. Balar said. Enfortumabe vedotin adverse events Side effects can include hyperglycemia within the first one or two cycles. Sometimes it’s asymptomatic, sometimes it’s accompanied by acid-base disturbances, and in very rare cases, it’s fatal. The problem is possibly linked to higher baseline body mass index. At least half of patients develop a sunburn-like rash, also within the first one or two cycles, that spares the face and can be pruritic. It’s manageable by topical steroids, oral antihistamines, dose reductions, or dose interruptions. “If anything severe is going to happen, it's going to happen within the first one or two cycles. I see [patients at] every visit” in the first two cycles “primarily to catch anything untoward,” Dr. Balar said. Neuropathy is the “most significant dose-limiting toxicity, and tends to develop about 4 months into treatment,” he said. Show notes written by M. Alexander Otto. Dr. Balar disclosed research, advisory, and/or speaker relationships with Genentech, Incyte, Bristol-Myers Squibb, Janssen, Merck, Pfizer, AstraZeneca, and other companies. Dr. Lyss writes a column for MDedge Hematology/Oncology called “” and had no other conflicts of interest. /episode/index/show/jcsopodcast/id/19106825

Gene therapies in hemophilia with Dr. Glenn Pierce 05/13/2021

Gene therapies in hemophilia with Dr. Glenn Pierce A “very basic” type of gene therapy could potentially cure hemophilia, but a major hurdle has been the lack of an effective mode of delivery. Recent strides in using adeno-associated virus (AAV) vectors are changing that, and Glenn Pierce, MD, World Federation of Hemophilia Vice President, Medical, predicts approvals in the next 12-18 months. Dr. Pierce shared his personal experience with hemophilia and discussed his and others’ ongoing research on the use of AAV-mediated gene therapy with host David Henry, MD, in this episode. Hemophilia and AAV gene therapy key points: Hemophilia is caused by a monogenic defect and could, theoretically, be cured by gene replacement or augmentation, says Dr. Pierce, who notes that “it sounds disarmingly simple, but behind that simplicity is a very complex procedure.” The approach uses “gene addition,” which is a basic gene therapy involving the addition of a normal gene to the variant in an individual. This ultimately corrects the clotting factor deficiency. The complexity is in getting the normal gene into the body where it can have the intended therapeutic effect. After more than 20 years of working to overcome that barrier, Dr. Pierce and others are finding success with using AAVs. The approach has some similarities to that used in developing the mRNA COVID-19 vaccines but requires the use of DNA established within the virus (rather than mRNA) to provide a more stable effect. Questions about how long it will last are currently being investigated. Multiple phase 3 trials are underway or completed. Data from two of those have been released in recent months, and the results are very encouraging: “It’s a remarkable achievement – many patients are doing well and, for all intents and purposes, could be considered free of [hemophilia],” Dr. Pierce says, adding that he would “potentially … use the ‘C word’ – cured – for at least a period of time.” The therapy is generally well tolerated. Efforts are ongoing to identify the best ways to proactively and reactively use prednisone to manage side effects such as mild increases in transaminase levels. To date, the risk-benefit profile appears reasonable for patients with clotting factor IX deficiency, and it is likely that the therapy in that setting “will march toward the regulatory process to determine if it’s safe and effective for approval,” he said. Responses in those with clotting factor VIII deficiency have been more variable, with some patients requiring long-term prednisone use, which is problematic. More information is needed about this, but investigation is ongoing, he said. Registries are available and many companies are involved in clinical trials. Clinicians and patients can look for information at clinicaltrials.gov, wfh.org (which publishes trial results and conducts workshops and meetings), and at the US National Hemophilia Foundation (Hemophilia.org) and the Society of Thrombosis and Hemostasis (ISTH.org). Show notes written by Sharon Worcester, MA, a reporter for MDedge and Medscape. Disclosures Dr. Henry has no relevant disclosures. Dr. Pierce disclosed relationships with Ambys Medicines, BioMarin, BridgeBio, CRISPR Therapeutics, Decibel Therapeutics, Frontera, Geneception, Generation Bio, Novo Nordisk, Pfizer, Regeneron, Third Rock Ventures, Voyager Therapeutics, Global Blood Therapeutics, VarmX SAB, the National Hemophilia Foundation Medical and Scientific Advisory Council, and the World Federation of Hemophilia. * * * For more MDedge Podcasts, go to Email the show: Interact with us on Twitter: David Henry on Twitter: /episode/index/show/jcsopodcast/id/19023368

Thrombosis and thrombocytopenia caused by COVID-19 vaccines: How to identify and treat VITT, VIPIT, or TTS 05/06/2021

Thrombosis and thrombocytopenia caused by COVID-19 vaccines: How to identify and treat VITT, VIPIT, or TTS At least 17 cases of thrombosis and thrombocytopenia have been reported in patients who received the Johnson & Johnson COVID-19 vaccine in the United States. Such events have been reported in patients who received the AstraZeneca vaccine as well. In this episode, , of the University of Pennsylvania, Philadelphia, tells host , how to identify and manage patients with these vaccine-induced events. What’s in a name? The phenomenon of vaccine-induced thrombosis and thrombocytopenia has been given different names, including: Vaccine-induced immune thrombotic thrombocytopenia (VITT) Vaccine-induced prothrombotic immune thrombocytopenia (VIPIT) Thrombosis and thrombocytopenia syndrome (TTS). Dr. Cuker’s preferred acronym is VITT. VITT is an immune-mediated reaction to the Johnson & Johnson and AstraZeneca vaccines that “results in thrombocytopenia and a strong propensity for thrombosis,” Dr. Cuker explained. Dr. Henry noted that VITT is reminiscent of heparin-induced thrombocytopenia (HIT). Incidence unclear VITT appears to be “very rare,” but “we still don't have a great sense of how common it is” because additional cases may not have been recognized or have yet to present, Dr. Cuker said. VITT occurs about 5-30 days after vaccination. VITT appears to be mediated by IgG antibodies, which take time to build up. The exact mechanism is unknown, but VITT could be related to the adenovirus vector used in the Johnson & Johnson and AstraZeneca vaccines, Dr. Cuker said. The first 15 cases of VITT associated with the Johnson & Johnson vaccine occurred in women, and most patients were aged under 50 years. In Canada, where the AstraZeneca vaccine is available, cases of VITT have been reported in patients in their 80s and 90s. Diagnosing VITT Symptoms of VITT can include severe, unrelenting headache; severe abdominal pain; nausea and vomiting; as well as typical signs and symptoms of deep vein thrombosis or pulmonary embolism. To determine if a patient has VITT, Dr. Cuker recommends ordering a disseminated intravascular coagulation panel – prothrombin time, partial thromboplastin time, fibrinogen, and D-dimer – as well as a standard HIT enzyme-linked immunosorbent assay (ELISA). Rapid immunoassays for HIT are not reliable for VITT, so HIT ELISA must be used, Dr. Cuker emphasized. Most patients with VITT have a “strongly positive” ELISA with optical density values “well in excess of 100 or 1.0,” depending on the scale, Dr. Cuker said. Manage VITT like HIT Patients should receive an anticoagulant, but not heparin, Dr. Cuker said. It isn’t clear if heparin will be harmful in patients with VITT, but current guidelines recommend avoiding heparin. He also advised against using warfarin or vitamin K antagonists in patients with VITT “at least until their platelet count recovers.” High-dose intravenous immunoglobulin (e.g., 1 g/kg for 2 consecutive days) is recommended, as it is believed to interfere with platelet activation. Show notes written by M. Alexander Otto, a reporter for MDedge and Medscape. Disclosures Dr. Henry has no relevant disclosures. Dr. Cuker has served as a consultant for Synergy Pharmaceuticals; has received authorship royalties from UpToDate; and his institution has received research support on his behalf from Alexion, Bayer, Novartis, Novo Nordisk, Pfizer, Sanofi, Spark Therapeutics, and Takeda. * * * For more MDedge Podcasts, go to Email the show: Interact with us on Twitter: David Henry on Twitter: /episode/index/show/jcsopodcast/id/18971069

Toward more personalized treatment in prostate cancer: The CCR score predicts metastasis and guides treatment decisions after radiation 04/29/2021

Toward more personalized treatment in prostate cancer: The CCR score predicts metastasis and guides treatment decisions after radiation The combined clinical cell-cycle risk (CCR) score uses clinical and genetic factors to assess the risk of metastasis after radiation therapy in patients with prostate cancer. The CCR score has proven accurate in studies and can guide post-radiation treatment decisions in practice, according to , of the University of Utah, Salt Lake City. Dr. Tward discusses the CCR score with host , in this episode. About the score The CCR score combines the cell-cycle progression (CCP) score (available commercially as the Prolaris test) and the Cancer of the Prostate Risk Assessment (CAPRA) score to more precisely determine the postradiation risk for metastatic disease. Investigators identified a threshold for determining precise risk levels (2.112), which allows for personalized treatment decision-making based on more individual characteristics than standard risk-group categorizations, according to Dr. Tward. He noted that standard risk groups can include a broad range of actual risk even within a given category. Risk groups are “reasonably good at prognosticating who may or may not go on to have metastasis etc., but they’re not that good,” Dr. Tward said. CCR score proves effective Dr. Tward and colleagues evaluated the CCR score in a retrospective study published in Clinical Genitourinary Cancer (). The study included 718 men with intermediate- or high-risk localized prostate cancer who received single modality or multimodality therapy. Results showed that patients with CCR scores below the identified threshold (2.112) could safely forgo multimodality therapy. CCR score bests other scoring systems In another study, the CCR score proved more accurate than other scoring systems. Dr. Tward presented findings from this study at the 2021 Genitourinary Cancers Symposium (). The study included 741 men with intermediate- or high-risk localized prostate cancer who received single modality or multimodality therapy. The CCR score predicted metastasis (hazard ratio, 2.21; C-index, 0.78) and did so better than National Comprehensive Cancer Network risk groups (C-index, 0.70), the CAPRA score alone (C-index, 0.71), or the CCP score alone (C-index, 0.69). Dr. Tward said he has used the CCR score in his own practice for years and found it helpful. Show notes written by Sharon Worcester, a reporter for MDedge and Medscape. Disclosures Both studies were funded by Myriad Genetics, the company that developed the Prolaris test. Dr. Tward disclosed relationships with Myriad Genetics and other companies. Dr. Henry has no relevant disclosures. * * * For more MDedge Podcasts, go to Email the show: Interact with us on Twitter: David Henry on Twitter: /episode/index/show/jcsopodcast/id/18895136

Changing perspectives: Dr. Michael Weiner recounts his experiences as an oncologist who became a cancer patient and then a caregiver 04/22/2021

Changing perspectives: Dr. Michael Weiner recounts his experiences as an oncologist who became a cancer patient and then a caregiver Pediatric oncologists are used to dealing with emotional, heart-wrenching situations, but oncology took on a new dimension for , when both he and his daughter were diagnosed with cancer. Dr. Weiner, a pediatric oncologist at Columbia University, New York, describes his roles as oncologist, patient, and caregiver to host , in this episode. Oncologist as patient: Lessons learned Dr. Weiner’s journey as a cancer patient began when he felt a lymph node on his neck that he knew wasn’t “normal.” A colleague examined Dr. Weiner and suggested the “watch-and-wait” approach, but Dr. Weiner insisted on immediate biopsy. The diagnosis was follicular lymphoma, and Dr. Weiner had a hard time accepting that his malignancy was treatable but not curable. One of the things Dr. Weiner learned as a cancer patient is that “you really need to connect with your doctor,” so he chose a doctor who felt like a good fit for him. Another lesson Dr. Weiner learned was that cancer can be very isolating. Though friends and family can offer help and support, “you take this journey alone,” he said. Dr. Weiner was treated with rituximab and radiation, which proved successful. It’s been 3 years since he completed his treatment. Dr. Weiner had been reluctant to undergo radiation because of the risk of thyroid cancer, and, unfortunately, he now has a small thyroid nodule that’s under observation. Update: After this episode was recorded, Dr. Weiner was diagnosed with papillary thyroid cancer. He is set to undergo a total thyroidectomy. Oncologist as caregiver: Taking a backseat Dr. Weiner’s daughter was diagnosed with papillary thyroid carcinoma after a nodule was found on a routine exam. Dr. Weiner and his daughter decided to educate themselves about her malignancy and opted for an aggressive course of treatment. “I tried very, very hard to be a parent and not a physician,” Dr. Weiner said. He decided to put his faith in her care team. “I in no way participated in the final decision-making,” he said. His daughter ultimately had a total thyroidectomy and high-dose radioactive iodine. The process, like his own cancer journey, was difficult. Dr. Weiner recounts these experiences in his book “Living Cancer: Stories from an Oncologist, Father, and Survivor,” which can be found here: . Show notes written by M. Alexander Otto, a reporter for MDedge and Medscape. Disclosures Dr. Weiner and Dr. Henry have no relevant disclosures. These show notes were updated on 4/22. * * * For more MDedge Podcasts, go to Email the show: Interact with us on Twitter: David Henry on Twitter: /episode/index/show/jcsopodcast/id/18794651

Optimizing CAR T-cell therapies in lymphoma: Improving response, fighting cytokine release syndrome, and identifying mechanisms of resistance 04/15/2021

Optimizing CAR T-cell therapies in lymphoma: Improving response, fighting cytokine release syndrome, and identifying mechanisms of resistance Studies have shown that chimeric antigen receptor (CAR) T-cell therapies produce responses in patients with relapsed/refractory B-cell lymphomas, but researchers continue to look for ways to improve efficacy, decrease toxicity, and overcome treatment resistance. , of Boston Children’s Hospital, discusses some of this research with host , in this episode. Dr. Kean outlines four recent studies of CAR T-cell therapies in lymphoma. The studies were selected as part of the “” session at the 2020 annual meeting of the American Society of Hematology. Primary Analysis of ZUMA-5: A Phase 2 Study of Axicabtagene Ciloleucel (Axi-Cel) in Patients with Relapsed/Refractory Indolent Non-Hodgkin Lymphoma This study was designed to assess the efficacy and safety of axicabtagene ciloleucel (axi-cel) in patients with indolent lymphomas. In follicular lymphoma, the overall response rate (ORR) was 94%, and the complete response (CR) rate was 80%. In marginal zone lymphoma, the ORR was 85%, and the CR rate was 60%. There was one grade 5 and one grade 4 case of cytokine release syndrome (CRS). Dr. Kean noted that 146 patients were evaluable for adverse events, so the single death related to CRS should be viewed in that context. Overall, 82% of patients had CRS of any grade. Jacobson C et al. ASH 2020, Abstract 700. . What’s involved in a CAR T-cell study? Dr. Kean explained that a patient is first deemed eligible by an oncologist and then enrolled in a CAR T-cell study. For studies like ZUMA-5 that are testing autologous CAR T cells, basic lab work is done to ensure the patient has a high enough lymphocyte count. The patient then undergoes apheresis, and the patient’s T cells are used to create the CAR T-cell product. The company developing the product transduces the T cells with the CAR so the resulting CAR T cells will target cancer cells. The therapy in ZUMA-5, axi-cel, targets CD19, which is expressed on B-cell lymphoma cells. Normal B cells express CD19 as well, so immunoglobulin replacement is sometimes necessary to offset the loss of normal B cells. Efficacy and Safety of Tisagenlecleucel in Adult Patients with Relapsed/Refractory Follicular Lymphoma: Interim Analysis of the Phase 2 ELARA Trial Tisagenlecleucel differs from axi-cel in the signaling domain, though tisagenlecleucel targets CD19 as well, Dr. Kean explained. She noted that tisagenlecleucel is a bit more long-lived than axi-cel. In this trial, tisagenlecleucel produced an ORR of 82% and a CR rate of 65%. There were no cases of grade 3 or higher CRS, which may be attributed to the different signaling domain, Dr. Kean said. Fowler NH et al. ASH 2020, Abstract 1149. . TRANSCEND CLL 004: Phase 1 Cohort of Lisocabtagene Maraleucel (liso-cel) in Combination with Ibrutinib for Patients with Relapsed/Refractory (R/R) Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) Patients in this study received the CAR T-cell therapy liso-cel in combination with the BTK inhibitor ibrutinib. The combination increased both efficacy and safety, as ibrutinib assisted in calming down the immune response. There were no grade 5 adverse events and no cases of grade 4 CRS or neurotoxicity. The ORR was 95%, and the CR rate was 63%. There was no difference in response among patients who had or had not received a BTK inhibitor previously, Dr. Kean noted. Wierda WG et al. ASH 2020, Abstract 544. . CD58 Aberrations Limit Durable Responses to CD19 CAR in Large B Cell Lymphoma Patients Treated with Axicabtagene Ciloleucel But Can Be Overcome Through Novel CAR Engineering Dr. Kean noted that CAR T-cell therapy typically produces a CR in more than 90% of patients within 30 days, but the long-term duration of response is about 50%. With this study, researchers wanted to investigate why a CAR T-cell therapy would fail and determine if any tumor-specific factors affect the duration of response. The team found that patients who had mutations in CD58 were less likely to achieve a CR to axi-cel, and most patients with these mutations ultimately progressed. CD2, the T-cell ligand for CD58, plays adhesive and costimulatory roles in T cells, and CAR T cells rely on intrinsic T-cell signaling to work, Dr. Kean explained. So if the CD2 in a CAR T cell can’t “see” CD58 on the tumor because of a mutation, the CAR T cell doesn’t work, she added. To bypass this, the researchers created a construct integrating CD2 costimulatory domains within the CAR molecule so it expressed CD2 in a way that doesn’t require CD58. The new construct “cures tumors like gangbusters” in mouse models, Dr. Kean said, adding that this CAR T-cell therapy could be coming to the clinic soon. Maizner RG et al. ASH 2020, Abstract 556. . Looking ahead: Concerns about cost Cost is a critical barrier to receiving CAR T-cell therapy, Dr. Kean noted, especially for patients who require additional treatment after receiving CAR T cells. The next generation of CAR T-cell research should determine if this treatment is best used as a bridge to transplant or if CAR T-cell therapy can stand alone, she added. To make the cost more palatable, CAR T-cell products should be a final cure, Dr. Kean said. Show notes written by Malika Gill, MD, a resident at Pennsylvania Hospital, Philadelphia. Disclosures Dr. Henry has no relevant disclosures. Dr. Kean disclosed relationships with Magenta Therapeutics, Bristol-Myers Squibb, Kymab, HiFiBiO Therapeutics, Regeneron, Novartis, Gilead, Bluebird Bio, and Forty Seven. * * * For more MDedge Podcasts, go to Email the show: Interact with us on Twitter: David Henry on Twitter: /episode/index/show/jcsopodcast/id/18712706

Trends in genetic testing for breast and ovarian cancer: Undertesting and racial/ethnic disparities persist 04/08/2021

Trends in genetic testing for breast and ovarian cancer: Undertesting and racial/ethnic disparities persist Researchers have tracked the evolution of genetic germline testing in women with breast or ovarian cancer in recent years and reported the results in the Journal of Clinical Oncology. Study author , of Stanford (Calif.) University, describes the group’s findings () to guest host Alan Lyss, MD, subprincipal investigator emeritus for Heartland Cancer Research NCORP, in this episode. Study rationale and methods Dr. Kurian said that an inflection point for breast cancer genetics was in 2013 when the U.S. Supreme Court ruled that gene patenting was not allowed for the purposes of genetic testing. As a result, the cost of testing BRCA1/2 genes fell, and testing became much more accessible. With their study, Dr. Kurian and colleagues aimed to look at trends following the increase in accessibility. The researchers used Surveillance, Epidemiology, and End Results Program (SEER) records of women aged 20 years and older who were diagnosed with breast or ovarian cancer from 2013 to 2017 in California or Georgia. The team linked these data to results of clinical germline testing through 2019. Dr. Kurian explained that the SEER data are comprehensive enough that all cancer cases in California and Georgia were likely included, the states provide a large catchment area of about 50 million people, and the states have different kinds of racial/ethnic diversity and urban/rural distribution. The researchers used the data to assess testing trends as well as rates of variants of uncertain significance (VUS) and pathogenic variants (PVs). Results by hypothesis Hypothesis 1: Multigene panels will entirely replace testing for BRCA1/2 only. This hypothesis was essentially correct. Testing of only two genes was almost totally replaced by testing many more genes. The number of genes tested for breast cancer increased annually by 28% over the study period. Hypothesis 2: Underutilization of testing patients with ovarian cancer will improve over time. It is standard of care to recommend genetic testing for all ovarian cancer patients. Based on 2013-2014 data, only one-third of women were tested. As tests became more accessible in subsequent years, the hope was that more women would be tested. Unfortunately, there was very little improvement in testing rates over the study period. Hypothesis 3: More patients will be tested at lower levels of pretest risk for PVs. In patients aged older than 60 years, testing rates increased for breast cancer (from 11% to 15%) and ovarian cancer (from 25% to 31%). Patients aged younger than 45 years had lower testing rates over time, however. Dr. Kurian noted that about 33% of ovarian cancer patients undergo genetic testing, but the goal is 100%. It is unclear if the goal should be 100% for breast cancer, Dr. Kurian said. Hypothesis 4: Sociodemographic difference in testing trends would not be seen. There was not much of a gap observed with breast cancer patients. For example, among patients with breast cancer, approximately 31% of those who had genetic testing were uninsured, 31% had Medicaid, and 26% had private insurance or Medicare. There is more of an equity issue with ovarian cancer. About 28% of those who had genetic testing were uninsured, 27% had Medicaid, and 39% had private insurance or Medicare. Dr. Kurian said disparities in ovarian cancer persist in patients who are uninsured and those in certain racial/ethnic groups, including African Americans. These patients are less likely to get genetic testing. Hypothesis 5: Detection of PVs and VUS will increase. The detection of VUS increased at a higher rate in comparison with PVs when more genes were being tested. This is likely because of the fact that, for every PV you find, you will find many more VUS, Dr. Kurian said. Hypothesis 6: Racial or ethnic disparities in rates of VUS will diminish over time. Disparities actually increased over the study period as more genes were tested. Some studies have suggested that VUS results lead to unnecessary prophylactic surgery, Dr. Kurian said. She added that the decision to undergo prophylactic surgery should not be based on a VUS because “the great majority of VUS turn out to be nothing.” Additional findings and implications for practice The study revealed that most PVs were in 20 genes associated with breast or ovarian cancer. Dr. Kurian and colleagues concluded that the way to improve testing is to focus on those 20 genes and ensure appropriate patients are being tested, rather than adding more genes to tests. Dr. Kurian said it is urgent to increase genetic testing in patients with ovarian cancer, as it is not being done at the rate it should be. Dr. Kurian also noted that one positive outcome of the COVID-19 pandemic has been an increase in telehealth visits and at-home genetic testing. Providing patients with these more convenient options could increase the use of genetic testing. Show notes written by Alesha Levenson, MD, a resident at Penn Medicine, Philadelphia. Disclosures Dr. Kurian disclosed relationships with Myriad Genetics, Ambry Genetics, Color Genomics, GeneDx/BioReference, InVitae, and Genentech. The study was supported by the National Cancer Institute, the Centers for Disease Control and Prevention, and the California Department of Public Health. Dr. Lyss writes a column for MDedge Hematology/Oncology called “Clinical Insights” (). He has no other conflicts of interest. * * * For more MDedge Podcasts, go to Email the show: Interact with us on Twitter: Dr. Lyss on Twitter: /episode/index/show/jcsopodcast/id/18637433

Improving cancer screening in the COVID era: Drive By Flu-FIT allows for socially distanced colorectal cancer screening 04/01/2021

Improving cancer screening in the COVID era: Drive By Flu-FIT allows for socially distanced colorectal cancer screening A program called Drive By Flu-FIT has allowed for socially distanced colorectal cancer (CRC) screening during the COVID-19 pandemic. Armenta Washington, senior research coordinator at the University of Pennsylvania, describes the program to guest host Alan Lyss, MD, subprincipal investigator emeritus for Heartland Cancer Research NCORP, in this episode. What is Drive By Flu-FIT? Drive By Flu-FIT is a socially distanced version of the Flu-Fecal Immunochemical Test (Flu-FIT) program. Flu-FIT was designed to increase access to CRC screening by offering take-home FIT tests to patients at the time of their annual flu shots. The goal of Drive By Flu-FIT is to provide a COVID-safe approach to CRC screening and counteract the decrease in CRC screening seen during the pandemic. Drive By Flu-FIT is a joint effort of the University of Pennsylvania, the Einstein Healthcare Network, Chi Eta Phi Sorority, and Enon Tabernacle Baptist Church, the largest Baptist church in the Philadelphia region. How does Drive By Flu-FIT work? To participate in a Drive By Flu-FIT event, community members had to complete eligibility, registration, and demographic questionnaires online. Patients who were enrolled watched a short educational video on CRC and completed two questionnaires – one on CRC screening knowledge (14 items) and one on screening intentions (5 items) – before and after watching the video. At the Drive By Flu-FIT events, patients remained in their cars while physicians in personal protective equipment handed out FITs and explained how to use them and return them. Patients could also receive a flu vaccine at each event. Results: High return rate According to initial data, 335 patients registered for a Drive By Flu-FIT event, but 80 (23.9%) ultimately didn’t attend and 63 (18.8%) were found to be ineligible. A total of 192 patients attended and received a FIT (57.3%). Scores on both questionnaires increased after patients watched the educational video. Patients’ baseline knowledge of CRC was high but lacking in four areas: risk factors for CRC, the optimal frequency of FITs, the link between Lynch syndrome and CRC, and the relationship between physical activity and CRC risk. Of the 192 patients who received a FIT, 38 (19.7%) did not return it. There were 141 patients (73.4%) with a negative FIT result, while 13 (6.7%) had a positive FIT result and were referred for colonoscopy. Resources For more information on Flu-FIT, visit . For more details on Drive By Flu-FIT, see: AACR Virtual Meeting: COVID-19 and Cancer, Abstract S02-04: . MDedge coverage of the meeting presentation: . Ms. Washington disclosed no conflicts of interest. The study was supported by the National Cancer Institute. The FITs were donated by Polymedco, and the flu vaccines were donated by the Philadelphia Public Health Department. Dr. Lyss writes a column for MDedge Hematology/Oncology called “Clinical Insights” (). He has no other conflicts of interest. * * * For more MDedge Podcasts, go to Email the show: Interact with us on Twitter: Dr. Lyss on Twitter: /episode/index/show/jcsopodcast/id/18536564

Unpacking von Willebrand disease guidelines: Dr. Paula James talks diagnosis and pre-procedure prophylaxis 03/25/2021

Unpacking von Willebrand disease guidelines: Dr. Paula James talks diagnosis and pre-procedure prophylaxis Earlier this year, clinical practice guidelines for the diagnosis and management of von Willebrand disease (VWD) were published in Blood Advances. The guidelines () are a collaborative effort from the American Society of Hematology, the International Society on Thrombosis and Haemostasis, the National Hemophilia Foundation, and the World Federation of Hemophilia. Guideline author , of Queens University, Kingston, Ont., reviews some of the recommendations in these guidelines with host , in this episode. Case discussion A patient presents with the complaint of heavy menstrual bleeding, which could indicate a bleeding disorder such as VWD. How does one diagnose or rule out VWD? Tests to order include CBC, prothrombin time (PT), and partial thromboplastin time (PTT). Results of CBC, PT, and PTT could be normal, which would necessitate special testing to specifically look at factor VIII and von Willebrand factor (VWF). A patient’s family history may be helpful, as most types of VWD are autosomal dominant, though two subtypes are recessive. Diagnostic evaluation of VWD VWF is the chaperone protein for factor VIII in the intrinsic pathway, which is measured by the PTT. In more severe forms of VWD, the PTT is prolonged because of factor VIII. VWF is measured separately because it is not reflected in the PT or PTT. The recommendation is to measure VWF antigen and employ a functional assay to see how well VWF binds platelets. The recommendation in the new guidelines is to use the GPIbM assay rather than the ristocetin cofactor assay. Many labs in the United States are still using the ristocetin cofactor assay. However, in Canada, Europe, and other parts of the world, many labs have moved to a newer assay that is automated. It has a much lower coefficient of variation and fewer issues with measurement of VWF in Black populations, which is a major issue with the cofactor assay. Types of VWD Type 1 VWD is characterized by a decreased amount of VWF. Type 1 patients have low VWF antigen and low platelet-dependent VWF function to a similar degree, with low or normal factor VIII. Type 2 VWD is characterized by aberrant VWF. The functional assay is a lot lower than VWF antigen. The platelet-dependent function to VWF antigen ratio cutoff is 0.7. Further testing is warranted to determine subtypes (2A, 2B, 2N, or 2M), including VWF multimers. Genetic testing can be helpful to further delineate subtypes. Type 3 VWD is characterized by the absence of VWF. The patient will have a VWF antigen level of 0, platelet-dependent VWF function of 0, and a reduced factor VIII level (usually less than 10%). Pregnant patients with VWD There is a protective adaptation in pregnancy, in which factors normalize in the third trimester, which works to prevent hemorrhage at delivery. This protective effect is because of the hormonal changes of pregnancy, and it is seen in patients with milder forms of VWD. WVF levels peak within 8-24 hours after delivery and then slowly return to baseline. There is a risk of delayed postpartum hemorrhage once VWF levels return to baseline, which tends to happen 7-14 days postpartum. Procedural planning: Desmopressin challenge test Desmopressin causes the release of VWF from the Weibel-Palade bodies of the endothelium, and it can be used as prophylaxis or treatment of bleeding in type 1 VWD. The desmopressin challenge test is used to check how the patient responds to desmopressin when well, to predict the patient’s response after an anticipated procedure. The test involves measuring VWF levels before desmopressin is given and at 1 hour, 2 hours, and 4 hours after desmopressin administration. The idea is to measure the magnitude of increase in VWF levels and observe how sustained that increase is to predict the patient’s response to desmopressin after future procedures. There is a subset of patients with type 1 VWD who have increased clearance of VWF that causes their decreased VWF levels. They may not have a sustained plateau in the VWF level after desmopressin, which emphasizes why testing as far as 4 hours after desmopressin administration is important. The dose of desmopressin given in this test is typically 0.3-0.4 mcg/kg. Recommendations for preprocedure prophylaxis for type 1 VWD Minor procedures (e.g., wisdom tooth extraction) The patient should receive an antifibrinolytic agent, such as tranexamic acid or aminocaproic acid, 2 hours before the procedure, followed by desmopressin 30-60 minutes prior to the procedure. After the procedure, the patient should continue to receive the antifibrinolytic agent for 3-4 days. Major procedures/surgeries (e.g., gallbladder removal) The guidelines do not recommend desmopressin for major procedures because patients need to be fluid-restricted for approximately 24 hours after administration because of the risk of hyponatremia. Desmopressin is a synthetic analog of vasopressin, which results in the accumulation of free water similarly to vasopressin. The guidelines do recommend giving VWF-containing concentrate to increase VWF and factor VIII to greater than 50% from baseline for at least 3 days. VWF concentrates can be given every 12 hours or as continuous intravenous infusions. Tranexamic acid should be given as an adjuvant both prior to the procedure and in the days following. Cryoprecipitate is not recommended because it can’t be virally inactivated. Preprocedure prophylaxis in type 2 or 3 VWD Desmopressin does not work for most patients with type 2 or 3 VWD. So even for minor procedures, these patients will need to receive VWF concentrate coupled with antifibrinolytics. Show notes written by Sheila DeYoung, DO, a resident at Pennsylvania Hospital, Philadelphia. Disclosures Dr. Henry has no relevant disclosures. Dr. James disclosed relationships with Baxter/Baxalta/Shire, CSL Behring, Bayer, and Octapharma. * * * For more MDedge Podcasts, go to Email the show: Interact with us on Twitter: David Henry on Twitter: /episode/index/show/jcsopodcast/id/18430388

FDA approvals in hematology and oncology, Part II: New oral formulations, RET and MET inhibitors, and CAR T-cell therapies 03/18/2021

FDA approvals in hematology and oncology, Part II: New oral formulations, RET and MET inhibitors, and CAR T-cell therapies We continue our review of drugs recently approved by the Food and Drug Administration (FDA) in the hematology/oncology space. In part 1 of our review, , of Pennsylvania Hospital, highlighted 11 therapies, including newly-approved treatments and new indications for older drugs. Part 1 was published Feb. 18 (). Now, in part 2, Dr. Mintzer tells host , about another 11 therapies recently approved by the FDA, including monoclonal antibodies, kinase inhibitors, chimeric antigen receptor (CAR) T-cell therapies, and more. Margetuximab-cmkb (Margenza) In Dec. 2020, margetuximab-cmkb was approved for use in combination with chemotherapy to treat adults with metastatic, HER2-positive breast cancer who had received at least two prior anti-HER2 regimens, including at least one for metastatic disease. Tafasitamab-cxix (Monjuvi) In July 2020, tafasitamab-cxix received accelerated approval for use in combination with lenalidomide to treat adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified, including DLBCL arising from low-grade lymphoma, who are not eligible for autologous stem cell transplant. Lurbinectedin (Zepzelca) In June 2020, lurbinectedin received accelerated approval to treat adults with metastatic small-cell lung cancer with disease progression on or after platinum-based chemotherapy. Belantamab mafodotin-blmf (Blenrep) In Aug. 2020, belantamab mafodotin-blmf received accelerated approval to treat adults with relapsed or refractory multiple myeloma who had received at least four prior therapies, including an anti-CD38 monoclonal antibody, a proteasome inhibitor, and an immunomodulatory agent. Umbralisib (Ukoniq) In Feb. 2021, the FDA granted umbralisib accelerated approval to treat adults with relapsed or refractory marginal zone lymphoma who had received at least one prior anti-CD20-based regimen and adults with relapsed or refractory follicular lymphoma who had received at least three prior lines of systemic therapy. Azacitidine tablets (Onureg) In Sept. 2020, the FDA approved azacitidine tablets for continued treatment of patients with acute myeloid leukemia who had achieved a first complete remission or complete remission with incomplete blood count recovery after intensive induction chemotherapy and who are not able to complete intensive curative therapy. Decitabine and cedazuridine tablets (Inqovi) In July 2020, the FDA approved an oral combination of decitabine and cedazuridine to treat adults with myelodysplastic syndromes (MDS). This includes previously treated and untreated, de novo and secondary MDS (including refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, and chronic myelomonocytic leukemia), as well as intermediate-1, intermediate-2, and high-risk MDS. Tepotinib (Tepmetko) In Feb. 2021, the FDA granted accelerated approval to tepotinib for adults with metastatic non-small cell lung cancer (NSCLC) harboring MET exon 14 skipping alterations. Pralsetinib (Gavreto) In Sept. 2020, pralsetinib received accelerated approval to treat adults with metastatic RET fusion-positive NSCLC. In Dec. 2020, the FDA granted full approval to pralsetinib to treat adult and pediatric patients ages 12 and older with advanced or metastatic RET-mutant medullary thyroid cancer who require systemic therapy or those with RET fusion-positive thyroid cancer who require systemic therapy and are refractory to radioactive iodine. Brexucabtagene autoleucel (Tecartus) In July 2020, the FDA granted accelerated approval to brexucabtagene autoleucel, a CD19-directed CAR T-cell therapy, for the treatment of adults with relapsed or refractory mantle cell lymphoma. Lisocabtagene maraleucel (Breyanzi) In Feb. 2021, another CD19-directed CAR T-cell therapy, lisocabtagene maraleucel, was approved to treat adults with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy. The approval encompasses DLBCL not otherwise specified (including DLBCL arising from indolent lymphoma), high-grade B-cell lymphoma, primary mediastinal large B-cell lymphoma, and follicular lymphoma grade 3B. Disclosures Dr. Mintzer and Dr. Henry have no relevant disclosures. * * * For more MDedge Podcasts, go to Email the show: Interact with us on Twitter: David Henry on Twitter: /episode/index/show/jcsopodcast/id/18346418

How I treat CLL and MCL: From ‘watch and wait’ to BCL2 and BTK inhibitors, CAR T-cell therapy, and transplant 03/11/2021

How I treat CLL and MCL: From ‘watch and wait’ to BCL2 and BTK inhibitors, CAR T-cell therapy, and transplant Treatments for chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL) have advanced in recent years, with more new developments on the horizon. , of the University of Pennsylvania, Philadelphia, reviewed some of these advances and future directions while describing how he would treat three patients. Host , posed the following cases for consideration. Case 1 In a 75-year-old male with no comorbid illness, routine blood work revealed a WBC count of 15,000/mcL. The manual differential showed mature lymphocytes and smudge cells. The patient has no constitutional symptoms, but there is suspicion of CLL. What to do? An incidental finding of elevated WBC is the most common presentation for CLL, Dr. Gerson noted. Flow cytometry is how most diagnoses are made. If the patient’s blood sample is CD5+ and CD20+, in the vast majority of cases, the patient has CLL. The main alternative diagnosis is MCL, so Dr. Gerson recommends checking for cyclin-D1 overexpression and translocation (11;14), which would be present in MCL. Dr. Gerson also recommends fluorescence in situ hybridization (FISH), cytogenetics, and next-generation sequencing to assist with prognostication. When the exam is normal and the patient is asymptomatic, no imaging is required. For this patient, treatment should be deferred until disease progression. Case 2 A 75-year-old, fit male has a WBC of 25,000/mcL, noted after the patient reported not feeling well, having a distended abdomen, night sweats, and weight loss. Blood work shows a hemoglobin level of 10.5 g/dL and a platelet count of 130 x 103/mcL. What to do? Because this patient is symptomatic, treatment is indicated, Dr. Gerson said. However, because of the pandemic, Dr. Gerson would likely delay therapy, perhaps until after COVID-19 vaccination. To assess risk, Dr. Gerson would perform immunohistochemistry, FISH, and next-generation sequencing in this patient. Patients with 17p deletion have high-risk disease, those with TP53 missense or nonsense mutations have even higher-risk disease, and patients with both a deletion and a mutation are “at excessively high risk,” Dr. Gerson said. He favors giving a BTK inhibitor to patients with TP53 mutation/17p deletion because of results from the CLL14 trial (N Engl J Med 2019; 380:2225-36. . However, because of the “small signal” in the trial, Dr. Gerson said plenty of his colleagues use a BTK inhibitor interchangeably with a BCL2 inhibitor and anti-CD20 therapy (e.g., venetoclax and obinutuzumab). Dr. Gerson said ibrutinib and acalabrutinib have similar efficacy, according to unpublished results of the ELEVATE-RR trial (). Both drugs inhibit platelets, and there appears to be a higher risk of atrial fibrillation with ibrutinib. Case 3 A 75-year-old, fit male has an elevated WBC, noted after complaints of bone pain, weight loss, night sweats, and enlarged lymph nodes. There is suspicion of MCL. What to do? MCL is a complicated disease and “incredibly” heterogeneous in clinical and pathological behavior, Dr. Gerson noted. The classic finding in MCL is cyclin-D1 overexpression caused by (11;14) translocation, but there are atypical translocations as well. The approach to first-line treatment of MCL varies and may include cytarabine-based induction, bendamustine plus rituximab, or rituximab alone. Brexucabtagene autoleucel, a chimeric antigen receptor T-cell therapy, is changing the landscape of treatment for relapsed/refractory MCL, Dr. Gerson said, as this treatment may offer a cure. Investigational therapies for MCL include the BTK inhibitor pirtobrutinib (LOXO-305) and hematopoietic stem cell transplant. Pirtobrutinib is under investigation in patients with MCL, CLL, and other indolent lymphomas that have progressed on or are intolerant to first-line therapy (Lancet. 2021 Mar 6;397[10277]:892-901. ). Show notes written by Ronak Mistry, DO, a resident at Pennsylvania Hospital, Philadelphia. Disclosures Dr. Gerson disclosed relationships with Loxo Oncology, Genentech, Pharmacyclics, and TG Therapeutics. Dr. Henry has no relevant disclosures. * * * For more MDedge Podcasts, go to Email the show: Interact with us on Twitter: David Henry on Twitter: /episode/index/show/jcsopodcast/id/18252560

COVID-19 vaccination in cancer patients: Who should be vaccinated and when? 03/04/2021

COVID-19 vaccination in cancer patients: Who should be vaccinated and when? When should cancer patients receive a COVID-19 vaccine? The National Comprehensive Cancer Network (NCCN) has issued recommendations to provide guidance on the topic. Guideline author , of Fred Hutchinson Cancer Research Center, Seattle, explains NCCN’s recommendations to host , in this episode. Prioritization Prioritization for COVID-19 vaccination should be given to cancer patients currently receiving chemotherapy, those who just finished active treatment, or those about to receive treatment. Additional factors that should be taken into consideration include age, comorbidities, and sociodemographic characteristics. Transplant and cellular therapy Patients who undergo allogeneic or autologous transplant or those who receive cellular therapy should be vaccinated at least 3 months after this treatment. This recommendation is based on best practices used for other vaccines, as there are insufficient data on COVID-19 vaccination in these patients, Dr. Pergam noted. Hematologic malignancies For patients with hematologic malignancies receiving intensive cytotoxic chemotherapy, vaccination should be delayed until absolute neutrophil count recovery. Patients with marrow failure from disease, those receiving therapy expected to have limited or no recovery, and those on long-term maintenance therapy should get vaccinated when a vaccine is available to them. Antibody response There are no current data to support checking antibodies prior to vaccination, as one will lose antibodies over time, Dr. Pergam noted. Likewise, there are no data to support testing for antibodies after vaccination. Solid tumor malignancies Patients with solid tumor malignancies who are receiving cytotoxic chemotherapy, targeted therapy, radiation, or checkpoint inhibitors or other immunotherapies should be vaccinated when a vaccine is available to them. For patients undergoing surgery, there should be adequate time between receiving a vaccine and the surgical date, as side effects from the vaccine, such as fever, can delay surgery. These guidelines are available for download from the NCCN website: . Show notes written by Malika Gill, MD, a resident at Pennsylvania Hospital, Philadelphia. Disclosures Dr. Pergam and Dr. Henry have no relevant disclosures. For more MDedge Podcasts, go to Email the show: Interact with us on Twitter: David Henry on Twitter: /episode/index/show/jcsopodcast/id/18159116

Managing pain in sickle cell crisis with Dr. Ifeyinwa Osunkwo 02/25/2021

Managing pain in sickle cell crisis with Dr. Ifeyinwa Osunkwo Ifeyinwa (Ify) Osunkwo, MD, MPH, joins us to talk about her approach to pain management in patients suffering from sickle cell crisis as well as the cognitive and behavioral effects of long-term opioid use in these patients. She and our host , cover these topics and more in this episode. is a professor of medicine at Atrium Health and the director of the Sickle Cell Enterprise at the Levine Cancer Institute, part of Atrium Health, in Charlotte, N.C. Over the course of a decade, the life expectancy of patients with sickle cell disease has increased. Today 99% of children with sickle cell disease will live to become adults. When treating patients with sickle cell pain it is important to consider their disease trajectory, and to weigh the pros and cons for initiation of opioid therapy. Management of sickle cell disease in the acute setting: In children, therapy usually includes use of intravenous fluid and intravenous opioids, then an eventual transition to oral opioids and NSAIDS. In adolescents, exposure to a prolonged course of high-dose opioids actually has been shown to exacerbate their pain. PCA (patient-controlled analgesia) versus “PRN” or as-needed medications removes the dependency on the external environment to receive pain medications and lessens the degree of psychological stress in these patients. Use of intravenous ketamine as an adjuvant to opioids in patients with an acute exacerbation has been shown to improve outcomes in patients (i.e., better pain control, decreased hospital stay, and management of anxiety and stress of a pain crisis.) In the acute pain setting, it is important to go through all differentials to get to where you are treating the right cause of pain. Following hospitalization, these patients often present back to the hospital in subacute opioid withdrawal. The key here is to engage patients in long term treatment plans. For opioid-induced itching, it has been shown that in patients who receive intravenous Benadryl have worse outcomes than in patients that receive oral Benadryl. Long-term side effects of chronic opioid therapy use: Psychological and behavioral side effects including insomnia, reduced libido, tolerance, oppositional behavior, poor memory, psychosis, paranoia, increased depression/anxiety and confusion. The opioid risk score is a helpful screening test that looks at the risk of adverse opioid outcomes. Specifically, family history of substance abuse, personal history of substance abuse, history of person abuse or psychological diagnosis results in a higher score which correlates with a higher risk of negative outcomes. Use of suboxone has proved to be very beneficial in patients on chronic opioid therapy in preventing frequent hospitalizations. Show notes written by Alesha Levenson, MD, a resident with Penn Medicine, Philadelphia. Disclosures Dr. Osunkwo disclosed relationships with Terumo, Global Blood Therapeutics, Acceleron, FORMA Therapeutics, Health Resources and Services Administration, Patient Centered Outcomes Research Institute, Micella Biopharma, Pfizer, and Novartis. Dr. Henry has no relevant disclosures. * * * For more MDedge Podcasts, go to Email the show: Interact with us on Twitter: David Henry on Twitter: /episode/index/show/jcsopodcast/id/18062207

FDA approvals in hematology and oncology: Novel agents and new tricks for old drugs 02/18/2021

FDA approvals in hematology and oncology: Novel agents and new tricks for old drugs In this episode, we review drugs recently approved by the Food and Drug Administration in the hematology/oncology space. , of Pennsylvania Hospital, joins host , to highlight some first-time approvals and new indications for older drugs. Approvals in 2020 Pembrolizumab (Keytruda) was approved for a range of new indications last year, including: First-line treatment of patients with unresectable or metastatic microsatellite instability–high or mismatch repair deficient colorectal cancer. Treatment of adult and pediatric patients who have tumor mutational burden–high (≥10 mutations/megabase) solid tumors that progressed after prior treatment and who have no satisfactory alternative treatment options. For use in combination with chemotherapy for the treatment of patients with locally recurrent unresectable or metastatic triple-negative breast cancer whose tumors express PD-L1 (combined positive score ≥10) as determined by an FDA-approved test. To treat patients with recurrent or metastatic cutaneous squamous cell carcinoma that is not curable by surgery or radiation. Avelumab (Bavencio) was approved for maintenance therapy in patients with locally advanced or metastatic urothelial carcinoma that has not progressed with first-line platinum-containing chemotherapy. Nivolumab (Opdivo) was approved for: Patients with unresectable advanced, recurrent, or metastatic esophageal squamous cell carcinoma after prior fluoropyrimidine- and platinum-based chemotherapy. Use in combination with ipilimumab as first-line treatment in adults with unresectable malignant pleural mesothelioma. Atezolizumab (Tecentriq) was approved in combination with cobimetinib and vemurafenib for patients with BRAF V600 mutation-positive unresectable or metastatic melanoma. Osimertinib (Tagrisso) was approved for adjuvant therapy after tumor resection in patients with non–small cell lung cancer whose tumors have EGFR exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test. Selinexor (Xpovio) was approved for: Use in combination with bortezomib and dexamethasone for the treatment of adults with multiple myeloma who have received at least one prior therapy. . Adults with relapsed or refractory diffuse large B-cell lymphoma not otherwise specified, including disease arising from follicular lymphoma, after at least two lines of systemic therapy. . The FDA also approved a new fixed-dose combination of pertuzumab, trastuzumab, and hyaluronidase-zzxf (Phesgo) for subcutaneous injection for: Use in combination with chemotherapy as neoadjuvant treatment of patients with HER2-positive, locally advanced, inflammatory, or early-stage breast cancer (either greater than 2 cm in diameter or node positive) as part of a complete treatment regimen for early breast cancer. Use in combination with chemotherapy as adjuvant treatment of patients with HER2-positive early breast cancer at high risk of recurrence. Use in combination with docetaxel to treat patients with HER2-positive metastatic breast cancer who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease. Relugolix (Orgovyx) was the first oral gonadotropin-releasing hormone receptor antagonist approved by the FDA for adults with advanced prostate cancer. Approvals in 2021 Cemiplimab-rwlc (Libtayo) was approved for patients with locally advanced or metastatic basal cell carcinoma previously treated with a hedgehog pathway inhibitor or for whom a hedgehog pathway inhibitor is not appropriate. Daratumumab plus hyaluronidase (Darzalex Faspro) was approved in combination with bortezomib, cyclophosphamide, and dexamethasone for newly diagnosed light chain amyloidosis. Approval in 2019 In late 2019, the FDA approved fam-trastuzumab deruxtecan-nxki (Enhertu) for patients with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens in the metastatic setting. Show notes written by Sheila DeYoung, DO, a resident at Pennsylvania Hospital, Philadelphia. Disclosures Dr. Mintzer and Dr. Henry have no relevant disclosures. * * * For more MDedge Podcasts, go to Email the show: Interact with us on Twitter: David Henry on Twitter: /episode/index/show/jcsopodcast/id/17977874

NCI-MATCH trial reveals actionable mutations and matches cancer patients to targeted therapies 02/11/2021

NCI-MATCH trial reveals actionable mutations and matches cancer patients to targeted therapies The NCI-MATCH trial was designed to reveal mutations in underexplored cancer types, allowing researchers to match patients to appropriate targeted therapies. Study investigator , from the National Cancer Institute, reviews the goals and results of NCI-MATCH with host , in this episode. Trial details NCI-MATCH has more than 1,000 participating sites. The trial is open to patients with advanced cancers that have progressed on standard treatment or rare cancers for which there is no standard treatment. Investigators use next-generation sequencing to identify mutations in tumor biopsies taken before the start of therapy. Sequencing is performed at MD Anderson Cancer Center, Houston; Massachusetts General Hospital, Boston; MoCha at NCI’s Frederick (Md.) National Lab; Yale University, New Haven, Conn.; and commercial labs. Matching patients to treatment When a patient is found to have an actionable mutation, that patient is assigned to an investigational treatment, typically monotherapy. A patient cannot be assigned to a treatment that is already known to be effective against their cancer; for example, patients with BRAF-mutated melanoma were excluded. The NCI’s Cancer Therapy Evaluation Program sends the patient's targeted therapy to the participating site within 24 hours of notification. CT imaging is done prior to the start of treatment, and patients are monitored with repeat scans every two cycles. Results Data on 5,954 patients with refractory malignancies were recently reported (). About 38% of those patients had an actionable mutation, and about 18% were assigned to a targeted therapy. Reports have shown varying response rates to matched therapy, ranging from 2% to 38%, Dr. Chen said. Results from the trial's treatment arms can be found here: . Dr. Chen noted that this trial was designed to match patients with single agents. Combination therapy has only been used in one arm of the study (). Future directions Nine treatment arms are still open, and one arm has yet to open. Conclusions are still pending the completion of the treatment arms. The next step for this research is expanding to include more combination therapies. There is also interest in comparing biopsies of tissue obtained at initial diagnosis and after treatment to further improve understanding of mutations. For more information on NCI-MATCH, visit: . . Show notes written by Sheila DeYoung, DO, a resident at Pennsylvania Hospital, Philadelphia. Disclosures Dr. Chen and Dr. Henry have no conflicts of interest. * * * For more MDedge Podcasts, go to Email the show: Interact with us on Twitter: David Henry on Twitter: /episode/index/show/jcsopodcast/id/17882216

COVID-19 vaccine 101: Dr. Drew Weissman discusses mechanisms, efficacy, and vaccinating patients with cancer or HIV 02/04/2021

COVID-19 vaccine 101: Dr. Drew Weissman discusses mechanisms, efficacy, and vaccinating patients with cancer or HIV How do the various COVID-19 vaccines work, and when should patients be vaccinated? We tackle these topics and more in this episode. Our host , is joined by , a professor at the University of Pennsylvania, Philadelphia. Dr. Weissman codeveloped the messenger RNA (mRNA) technology being used in the COVID-19 vaccines produced by Pfizer/BioNTech and Moderna. History of mRNA vaccines Testing of mRNA vaccines began in the 1990s. An initial problem with these vaccines was that the RNA was highly inflammatory. Dr. Weissman and his colleague, Katalin Karikó, PhD, discovered how to fix that problem in 2005. The pair found that placing modified nucleosides into mRNA made it noninflammatory and allowed for increased production of protein from the RNA – up to a 1,000-fold increase in mice. This technology is the basis of the Moderna and Pfizer/BioNTech COVID-19 vaccines. Immunology and vaccines To produce a good immune response, antigen must be present for a long time, though the optimal amount of time is unknown, Dr. Weissman said. The mRNA lipid nanoparticles (LNPs) used in the COVID-19 vaccines make protein for 10-14 days, resulting in a “great” immune response, according to Dr. Weissman. Most vaccines have an adjuvant, or something that stimulates the immune response by inducing TH1 or TH2 responses. The LNP used in the COVID-19 vaccines is an adjuvant that makes a specialized CD4 helper cell that drives antibody production, increases antibody affinity, and matures antibodies to make long-lived plasma cells to allow for long-lived antibody responses. This is the only adjuvant known that induces these type of helper T cells. COVID-19 vaccine reactions Adverse reactions to COVID-19 vaccination – flu-like symptoms, arm pain, etc. – are caused by the LNP, not the spike protein. Once the LNP is gone, usually within the first 24 hours, symptoms dissipate. The amount of spike protein produced decreases over 14 days. It’s unclear if patients should take NSAIDs to manage symptoms after COVID-19 vaccination, as this hasn’t been tested. However, with influenza vaccination, taking an NSAID will decrease the immune response. Variants and their impact on vaccination SARS-CoV-2 variants have been reported in Brazil, South Africa, California, and the United Kingdom. Dr. Weissman explained that there are two kinds of variation: when a virus learns how to better infect people and when the virus learns to avoid immune responses. Most SARS-CoV-2 variants are equally addressed by the vaccines, though we know vaccines have reduced efficacy against the South African variant, Dr. Weissman said. The good news is that coronavirus mutates very slowly, and it’s easy with mRNA vaccines to “plug in” a mutant and make a more effective vaccine, Dr. Weissman said. Vaccinating cancer patients: Treatment considerations For patients receiving chemotherapy: We don’t know the best time to administer COVID-19 vaccines to patients on chemotherapy, as this hasn’t been studied, Dr. Weissman said. When other vaccines were given to subjects receiving chemotherapy, those vaccines did not work as well. Chemotherapy knocks down myeloid cells around day 7, with recovery typically around day 28. Dr. Weissman said he would probably vaccinate at day 14 in the chemotherapy cycle, as the germinal centers where B cells are produced form about 2-7 days after receipt of the vaccine. For patients receiving checkpoint inhibitors: The optimal time for vaccination in patients receiving checkpoint inhibitors is unknown. However, the immune response to vaccination in patients on checkpoint inhibitors is expected to be similar to the general population or slightly enhanced. For patients receiving anti-CD20 antibodies: Anti-CD20 antibodies might blunt the B-cell response to vaccination. Rituximab, for example, depletes B cells in the circulation for months. In the absence of B cells, there won’t be a good antibody response. T-cell response is also stimulated by COVID-19 vaccines, but we don’t know how effective that response will be in protecting against infection, Dr. Weissman said. Vaccinating HIV patients Patients with well-controlled HIV (i.e., low viral load and CD4 counts >200) should generate a good immune response, Dr. Weissman said. Patients with poorly controlled HIV (i.e., high viral loads and low CD4 counts) are likely to have a poor immune response to vaccination, though it isn’t clear how poor the response will be. Should patients who recently had COVID-19 get vaccinated? Clinicians are waiting 90 days to vaccinate patients who have a positive COVID-19 test, Dr. Weissman said. In 95% of cases, SARS-CoV-2 infection conveys protective antibodies for at least 3 months. Patients with recent SARS-CoV-2 infection have more severe adverse reactions to vaccination (e.g., fever, arm pain, flu-like symptoms). It’s safe to wait until 2 weeks after recovery from infection before receiving the vaccine, and vaccination is expected to work well with a boosted immune response, Dr. Weissman said. Is there any role for checking antibody status after vaccination? Phase 3 trials of the Pfizer/BioNTech and Moderna vaccines showed that levels of neutralizing antibodies were higher in vaccinated patients than in those who had recently been infected; i.e., vaccines give a better immune response than infection. The durability of response to the vaccines is unknown, but studies are underway. The challenge for clinicians is that the antibody assays available are not directed at the spike protein, and they are not quantitative. Vaccine on the horizon The COVID-19 vaccine under development by Johnson & Johnson uses adenovirus. The spike protein is inserted into the genome of the adenovirus, and the virus is altered so it cannot replicate, thus preventing its spread. The live virus stimulates the cells to make a better immune response. This type of vaccine is potent and produces lower antigen levels than mRNA vaccines but with better T-cell responses, Dr. Weissman said. On Jan. 29, Johnson & Johnson released phase 3 data for this vaccine (). The vaccine was reported to be 85% effective overall in preventing severe COVID-19. Show notes written by Sheila DeYoung, DO, a resident at Pennsylvania Hospital, Philadelphia. Disclosures Dr. Weissman disclosed royalties from Moderna and Pfizer/BioNTech. Dr. Henry has no disclosures. * * * For more MDedge Podcasts, go to Email the show: Interact with us on Twitter: David Henry on Twitter: /episode/index/show/jcsopodcast/id/17699618

Barriers to clinical trial enrollment for patients with gynecologic cancers: Why patients don’t participate and how to improve enrollment 01/28/2021

Barriers to clinical trial enrollment for patients with gynecologic cancers: Why patients don’t participate and how to improve enrollment The greatest barrier to clinical trial enrollment is patients not knowing an appropriate trial exists, according to a survey of gynecologic cancer survivors. The most common reason survey respondents gave for not enrolling in clinical trials was that their medical team didn't tell them about any trials. and – who are both patient advocates and ovarian cancer survivors – conducted this survey and presented the results at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer last year (). Ms. Ellis discussed the survey results and other related research with host , in this episode. Ms. Ellis and Ms. Scroggins distributed their 26-question survey online. The survey was completed by 189 survivors of gynecologic cancers. Most respondents (65.6%) had never participated in a clinical trial. Reasons for nonparticipation included: The medical team never discussed trial participation (50.4%) The patient didn’t qualify for a trial (14.4%) The trial location was too far away (7.2%) The desired trial wasn’t available (4.0%) Insurance didn’t cover trial participation (1.6%) The patient didn’t want to receive a placebo (11.2%), wasn’t interested in experimental therapies (3.2%), didn’t want to be randomized (2.4%), or didn’t trust the medical system (1.6%) Other reason (fill in the blank; 38.4%). Roughly a third of respondents (34.4%) had participated in a clinical trial. Most of these respondents (86.2%) learned about the trial from their doctor. All past trial participants said they would participate again (84.6%) or they were not sure about future participation (15.4%). Ms. Ellis also mentioned a recent review and meta-analysis, which showed that more than half of all cancer patients offered a clinical trial do participate (J Natl Cancer Inst. 2020 Oct 6. doi: 10.1093/jnci/djaa155. ). Together, these finding suggests cancer patients may be willing to participate in trials but often don’t know that relevant trials exist. Ms. Ellis noted that her colleague, Ms. Scroggins, often says, “Patients can't go to the party if they don't get an invitation.” Disclosures Ms. Ellis, Ms. Scroggins, and Dr. Henry have no conflicts of interest. * * * For more MDedge Podcasts, go to Email the show: Interact with us on Twitter: David Henry on Twitter: /episode/index/show/jcsopodcast/id/17698253

Convalescent plasma for COVID-19, race linked to cancer-associated thrombosis risk, iron deficiency common in pregnancy, and more from ‘Best of ASH’ 01/21/2021

Convalescent plasma for COVID-19, race linked to cancer-associated thrombosis risk, iron deficiency common in pregnancy, and more from ‘Best of ASH’ New studies have shed additional light on how convalescent plasma may affect patients with COVID-19, how blood type impacts bleeding risk, the effects of race on cancer-associated thrombosis, and iron deficiency in pregnancy. These studies were presented as part of the “” session at the 2020 annual meeting of the American Society of Hematology. , of the University of North Carolina at Chapel Hill, who cochaired the session, reviews these studies with host , in this episode. Abstract #572: Association of ABO Blood Group with Bleeding Severity in Patients with Bleeding of Unknown Cause. . This study, which included 422 patients, indicated that blood group O is overrepresented in patients with bleeding of unknown cause. Blood group O was associated with a more severe bleeding phenotype, especially oral mucosal bleeding, independent of the levels of von Willebrand factor and factor VIII. Patients with blood group O had increased clot density, but blood group O didn’t influence thrombin generation or platelet function analysis. The researchers said these findings are important for better understanding the underlying mechanisms of bleeding in patients who have bleeding of unknown cause. Dr. Wolberg said this study reframed how people look at bleeding of unknown cause. Abstract #203: Racial/Ethnic Disparities in Cancer-Associated Thrombosis: A Population-Based Study. . This study included more than 942,109 cancer patients. Results showed an independent association between race/ethnicity and the risk of cancer-associated thrombosis. Asians/Pacific Islanders had a significantly lower incidence of cancer-associated thrombosis, compared with non-Hispanic Whites. African Americans had a significantly higher incidence of cancer-associated thrombosis versus non-Hispanic Whites. Racial/ethnic differences were especially prominent when examining pulmonary embolism only. It’s hard to determine what causes these differences, Dr. Wolberg said. The differences could be explained by underlying biological traits, systemic racism, access to care, and/or the severity of underlying comorbidities, according to the researchers. Abstract #424: Suboptimal Iron Deficiency Screening in Pregnancy in a High Resource Setting. . The study included data on 47,590 pregnancies in 44,552 women from Ontario. About 40% of these patients (n = 25,880) had ferritin measurements taken during pregnancy. Iron deficiency was observed in 52.8% of evaluable pregnancies, and severe iron deficiency was seen in 23.8%. These findings suggest a ferritin test should be included as part of routine bloodwork at the first prenatal visit, the researchers said. They also noted that failing to evaluate iron stores in the second and/or third trimester misses the periods of highest iron-deficiency risk, when intravenous iron may be considered. The researchers said these gaps in care should be addressed by revising guidelines. Abstract #245: Efficacy of COVID-19 Pathogen-Inactivated Convalescent Plasma for Patients with Moderate-to-Severe Acute COVID-19: A Case-Matched Control Study. . For this study, researchers compared 15 cases and 30 controls, all of whom had COVID-19. Cases received two units of COVID-19 convalescent plasma (CCP) from different donors. CCP appeared to improve survival in hospitalized COVID patients, though the difference was not significant. The 28-day mortality rate was 6.7% among cases and 20.7% in controls (P = .233). The researchers also found that unselected CCPs have heterogeneous antivirus activity. Pathogen reduction treatment did not impact antivirus activity. ADAP, ACE2, RVPN, and COVAM could be used to define activity. A posttransfusion increase in activity could be detected in some, but not all, patients. The researchers said more definitive studies are needed. *Some of the data presented at the meeting differ from data included in the abstracts. Disclosures: Dr. Wolberg disclosed relationships with Bristol-Myers Squibb, GlaxoSmithKline, and Takeda. Dr. Henry has no financial disclosures relevant to this episode. * * * For more MDedge Podcasts, go to Email the show: Interact with us on Twitter: David Henry on Twitter: /episode/index/show/jcsopodcast/id/17621048

Thrombosis research from ASH 2020: Khorana score falls short in cancer study, factors predict VTE in cancer patients with COVID-19, and antithrombotics don’t affect severe COVID outcomes 01/14/2021

Thrombosis research from ASH 2020: Khorana score falls short in cancer study, factors predict VTE in cancer patients with COVID-19, and antithrombotics don’t affect severe COVID outcomes Three studies revealed new findings on thrombosis in patients with cancer and/or COVID-19. These studies were presented at the 2020 annual meeting of the American Society of Hematology. One study suggested the Khorana score may be ineffective for predicting venous thromboembolism (VTE) in cancer patients. Another study revealed factors that can predict VTE in patients with cancer and COVID-19. And a third study indicated that antithrombotic agents don’t improve outcomes in patients with severe COVID-19. , of Washington University, St. Louis, reviews these studies with host , in this episode. Abstract 202: Performance of Khorana Score to Predict One-Year Risk of Venous Thromboembolism in Over Two Million Patients With Cancer. . The study included 2,112,260 patients with cancer. At 1 year after diagnosis, 227,170 (10.8%) patients had developed VTE. The Khorana score was a weak to modest predictor of the 1-year risk of VTE (area under the curve, 0.565; 95% confidence interval, 0.564-0.566). Abstract 204: Incidence of and Risk Factors for Venous Thromboembolism Among Hospitalized Patients With Cancer and COVID-19: Report From the COVID-19 and Cancer Consortium (CCC19) Registry. . The study included 1,813 hospitalized patients with COVID-19 and cancer who were enrolled in the CCC19 registry. Patients had an increased risk of VTE if they had received anticancer therapy in the last 3 months (odds ratio, 1.63), had active disease (OR, 1.25 for stable/responding disease and 1.67 for progressing disease), had a cancer subtype with a high VTE risk (OR, 1.57 for high risk and 3.42 for very high risk), or were admitted to the ICU within 48 hours of hospitalization (OR, 2.38). Patients had a reduced risk of VTE if they received preadmission anticoagulant (OR, 0.80) or antiplatelet therapy (OR, 0.71). The researchers said this information will aid the development of a risk prediction tool for VTE in hospitalized patients with cancer and COVID-19. For more information on the CCC19 registry, listen to the Blood & Cancer episode, “Studying cancer patients with COVID-19: NCCAPS and CCC19.” . Abstract 206: Anticoagulant and Antiplatelet Use not Associated With Improvement in Severe Outcomes in COVID-19 Patients. . This retrospective study included 28,076 patients with confirmed COVID-19 – 1,024 of whom were on antiplatelet agents, anticoagulants, or both. Chronic anticoagulant or antiplatelet use was not associated with a significantly lower risk of VTE (OR, 1.44), emergency department visit (OR, 0.94), ICU stay (OR, 0.87), or death (OR, 0.91). However, anticoagulant or antiplatelet use was associated with a decreased risk of ventilator use (OR, 0.72). Overall, these findings suggest chronic anticoagulant or antiplatelet use don't mitigate disease severity in COVID-19 patients, the researchers concluded. The session in which these abstracts were presented is entitled, “904. Outcomes Research – Non-Malignant Conditions: Venous Thromboembolism Associated With Cancer and/or COVID-19,” and details can be found here: . Data in some of the abstracts differ from data presented at the meeting. Disclosures Dr. Sanfilippo disclosed relationships with Covington & Burling, Luther & Associates, Bayer, Health Services Advisory Group, and Amgen. Dr. Henry has no relevant disclosures. * * * For more MDedge Podcasts, go to Email the show: Interact with us on Twitter: David Henry on Twitter: /episode/index/show/jcsopodcast/id/17519504

Highlights from SABCS 2020: New data on CDK4/6 inhibitors, omitting chemotherapy and radiotherapy, underreporting toxicity, and predicting outcomes in breast cancer 01/07/2021

Highlights from SABCS 2020: New data on CDK4/6 inhibitors, omitting chemotherapy and radiotherapy, underreporting toxicity, and predicting outcomes in breast cancer A number of groundbreaking and practice-changing studies were presented at the San Antonio Breast Cancer Symposium 2020. The RxPONDER, ADAPT, and PRIME-2 trials revealed patients who can forgo chemotherapy or radiotherapy, monarchE and PENELOPE-B showed conflicting results with CDK4/6 inhibitors, one study indicated that a new tool can guide adjuvant chemotherapy, and another study suggested that circulating tumor cells (CTCs) can predict overall survival (OS). , subprincipal investigator for Heartland Cancer Research NCORP, joined host , to discuss these and other studies — their top 10 presentations from SABCS 2020 — in this episode. 1. Abstract GS3-07. Identifying patients whose symptoms are under-recognized during breast radiotherapy: Comparison of patient and physician reports of toxicity in a multicenter cohort. This presentation could be one of the most important stories to emerge from SABCS 2020, according to Dr. Lyss. The trial included 9,868 breast cancer patients who received radiotherapy over an 8-year period. Investigators compared patient and physician reports of toxicity during radiotherapy, assessing four symptoms: pain, pruritus, edema, and fatigue. Physicians under-recognized moderate to severe pain 30.9% of the time, pruritus 36.7% of the time, edema 51.4% of the time, and fatigue 18.8% of the time. “The bottom line is: We’ve got to do better at this, and the first step in correcting it is to acknowledge that there is a problem. This abstract established that,” Dr. Lyss said. 2. Abstract GS2-03. Prime 2 randomised trial (postoperative radiotherapy in minimum-risk elderly): Wide local excision and adjuvant hormonal therapy +/- whole breast irradiation in women =/> 65 years with early invasive breast cancer: 10-year results. The trial enrolled 1,326 women with histologically confirmed, unilateral invasive, hormone receptor-positive (HR+) breast cancer who were all 65 or older, had a tumor measuring 3 cm or less, had no nodal involvement, and were about to undergo breast-conserving surgery. The women were randomized 1:1 to receive adjuvant whole-breast irradiation or no radiotherapy in addition to adjuvant endocrine therapy. At 10 years, the rate of ipsilateral recurrence was significantly lower with radiotherapy than without it (0.9% vs 9.8%, P = .00008). The 10-year rate of regional recurrence was significantly lower with radiotherapy as well (0.5% vs. 2.3%, P = .014). There was no significant difference in the radiotherapy and no-radiotherapy arms when it came to distant recurrence (3.6% vs. 1.9%, P = .07), contralateral recurrence (2.2% vs. 1.2%, P = .20), non–breast cancer (8.7% vs. 10.2%, P = .41), metastasis-free survival (96.4% vs. 98.1%, P = .28), or OS (81.0% vs. 80.4%, P = .68). These results suggest radiotherapy could be omitted in this patient population, but the decision should be discussed and tailored to the individual patient, according to Dr. Henry. 3. Abstract GS1-01. Primary outcome analysis of invasive disease-free survival for monarchE: abemaciclib combined with adjuvant endocrine therapy for high-risk early breast cancer. The monarchE trial enrolled 5,637 women with HR+, HER2- early breast cancer. Cohort 1 included patients with four or more positive nodes, up to three positive nodes and a tumor size ≥ 5 cm, or grade 3 disease. Cohort 2 included women with up to three positive nodes and a Ki-67 index ≥ 20%. Patients in both cohorts were randomized to standard endocrine therapy alone or standard endocrine therapy with abemaciclib. The 2-year rate of invasive disease-free survival (IDFS) was 92.3% in the abemaciclib arm and 89.3% in the control arm (P = .0009). The 2-year distant relapse-free survival rate was 93.8% and 90.8%, respectively (P = .0009). Dr. Lyss said this is the first real advance in HR+ breast cancer adjuvant treatment in many years and has the potential to save thousands of lives. However, these are early data and should be interpreted with caution. 4. Abstract GS1-02. Phase III study of palbociclib combined with endocrine therapy (ET) in patients with hormone-receptor-positive (HR+), HER2-negative primary breast cancer and with high relapse risk after neoadjuvant chemotherapy (NACT): First results from PENELOPE-B. The PENELOPE-B trial enrolled 1,250 women who had completed neoadjuvant chemotherapy and locoregional therapy. They were randomized to palbociclib plus endocrine therapy or endocrine therapy plus placebo. There was no significant difference in IDFS with palbociclib or placebo at 2 years (88.3% vs. 84%), 3 years (81.2% vs. 77.7%), or 4 years (73% vs. 72.4%). 5. Abstract GS4-10. Development and validation of a tool integrating the 21-gene recurrence score and clinicopathologic features to individualize prognosis for distant recurrence and prediction of absolute chemotherapy benefit in early breast cancer. The RSClin tool integrates the 21-gene recurrence score and clinicopathologic features, including the grade of the tumor, the tumor size, and the patient's age. Researchers found that RSClin could guide adjuvant chemotherapy in HR+, HER2-, axillary node-negative breast cancer with greater precision, when compared with clinicopathologic features or genomic data alone. RSClin is available at . 6. Abstract GS4-08. Clinical utility of repeated circulating tumor cell (CTC) enumeration as early treatment monitoring tool in metastatic breast cancer (MBC) - a global pooled analysis with individual patient data. This study included 4,079 metastatic breast cancer patients who had undergone baseline and follow-up CTC measurements in previous trials. The investigators analyzed changes in CTC levels between baseline and follow-up to determine whether those levels were associated with OS. The median OS was 47 months for patients who were CTC-negative at both baseline and follow-up, 32.2 months for patients who were positive at baseline and negative at follow-up, 29.6 months for patients who were negative at baseline and positive at follow-up, and 17.8 months for patients who were positive at both time points. With the negative-negative group as the reference, hazard ratios were 1.52 for the positive-negative group, 1.74 for the negative-positive group, and 3.15 for the positive-positive group (P < .0001 for all). 7. Abstract GS3-00. First results from a phase III randomized clinical trial of standard adjuvant endocrine therapy (ET) +/- chemotherapy (CT) in patients (pts) with 1-3 positive nodes, hormone receptor-positive (HR+) and HER2-negative (HER2-) breast cancer (BC) with recurrence score (RS) < 25: SWOG S1007 (RxPonder). RxPONDER included 5,083 adults with HR+, HER2- breast cancer, one to three positive nodes, no contraindications to taxane and/or anthracycline-based chemotherapy, and recurrence scores of 25 or below. Patients were randomized 1:1 to receive endocrine therapy or chemo-endocrine therapy using three stratification factors: recurrence score (0-13 vs.14-25), menopausal status, and axillary nodal dissection vs. sentinel node biopsy. At a median follow-up of 5.1 years, there was no association between chemotherapy benefit and recurrence score values in the whole study population. In postmenopausal patients, there was no difference in 5-year IDFS between patients who received chemotherapy and those who didn’t (91.6% vs. 91.9%, P = .82). However, in premenopausal patients, the 5-year IDFS rate was 94.2% with chemotherapy and 89% without it (P = .0004). The data also showed an OS benefit with chemotherapy in premenopausal patients (P = .032), although this result is considered early due to few deaths at the time of evaluation. “These data really establish that postmenopausal women with between one to three involved nodes and an Oncotype DX score of 25 or less do not need post-operative adjuvant chemotherapy; end of discussion,” Dr. Lyss said. “For physicians who have been giving those women chemotherapy, these data are immediately practice- changing.” 8. Abstract GS4-04. Endocrine therapy alone in patients with intermediate or high-risk luminal early breast cancer (0-3 lymph nodes), Recurrence Score <26 and Ki67 response after preoperative endocrine therapy: Primary outcome results from the WSG-ADAPT HR+/HER2- trial. In this phase 3 trial, researchers combined static biomarkers (recurrence score in baseline core biopsy) and dynamic biomarkers (Ki-67 response) in an attempt to optimize adjuvant therapy in luminal early breast cancer. The trial included 4,691 patients with HR+, HER2-negative, clinically high-risk disease who received about a month of standard endocrine therapy as neoadjuvant treatment. Patients with a pretreatment recurrence score of 0-11 continued endocrine therapy alone with no planned chemotherapy at all. Patients with a pretreatment recurrence score of 12-25 received their month of endocrine therapy and then had a core biopsy of their residual tumor. If the Ki-67 had dropped to less than 10%, the patient continued endocrine therapy alone. If the Ki-67 remained > 10% or the patient had clinical N2 or N3 lymph nodes, the patient was assigned to receive neoadjuvant chemotherapy. The 5-year IDFS rate was 92.6% in patients with a recurrence score of 12-25 and a Ki-67 response and 93.9% in patients with a recurrence score of 0-11. The 5-year distant relapse-free survival was 95.6% and 96.3%, respectively. The 5-year OS was 97.3% and 98%, respectively. These results suggest Oncotype DX testing could spare the majority of HR+, HER2- patients with zero to three positive lymph nodes from receiving chemotherapy, Dr. Lyss said. 9. Abstract GS3-01. Additional efficacy endpoints from the phase 3 KEYNOTE-355 study of pembrolizumab plus chemotherapy vs placebo plus chemotherapy as first-line therapy for locally recurrent inoperable or metastatic triple-negative breast cancer. In KEYNOTE-355, 847 patients with locally recurrent, inoperable or metastatic triple-negative breast cancer were randomized to receive pembrolizumab plus chemotherapy or chemotherapy plus placebo. Chemotherapy consisted of nab-paclitaxel, paclitaxel, or gemcitabine plus carboplatin. The median progression-free survival (PFS) was longer in the pembrolizumab arm, at 7.5 months, versus 5.6 months with chemotherapy alone (hazard ratio, 0.82). The PFS was superior with pembrolizumab regardless of the chemotherapy partner. However, higher PD-L1 expression was associated with a longer PFS, a higher overall response rate, and a longer duration of response. 10. Abstract GS3-06. Biomarker evaluation in the phase 3 ASCENT study of sacituzumab govitecan versus chemotherapy in patients with metastatic triple-negative breast cancer. Trophoblast cell-surface antigen-2 (Trop-2) is highly expressed in triple-negative breast cancer. Sacituzumab govitecan (SG) consists of an anti-Trop-2 antibody coupled to SN-38, an active metabolite of irinotecan. In the ASCENT trial, patients with metastatic triple-negative breast cancer were randomized to SG or standard single-agent chemotherapy. A subgroup analysis of this trial showed that Trop-2 levels correlated with PFS and OS. Patients were divided into three groups by Trop-2 levels — low (H-score <100), medium (100-200), and high (200-300). In patients with low Trop-2 levels, the median PFS was 2.7 months with SG and 1.6 months without it. The median OS was 9.3 months and 7.6 months, respectively. In patients with medium Trop-2 levels, the median PFS was 5.6 months with SG and 2.2 months without it. The median OS was 14.9 months and 6.9 months, respectively. In patients with high Trop-2 levels, the median PFS was 6.9 months with SG and 2.5 months without it. The median OS was 14.2 months and 6.9 months, respectively. *Some of the numbers mentioned in this episode are incorrect, but the correct numbers are reflected in the show notes. The data presented at SABCS 2020 sometimes differed from data included in the abstracts. Disclosures: Dr. Henry has no financial disclosures relevant to this episode. Dr. Lyss writes a column for MDedge Hematology/Oncology called “.” He has no other conflicts of interest. * * * For more MDedge Podcasts, go to Email the show: Interact with us on Twitter: David Henry on Twitter: /episode/index/show/jcsopodcast/id/17447399

Best of Blood & Cancer 2020 12/24/2020

SABCS 2020: More women may forgo chemo, surgery's role in opioid use, and pregnancy after breast cancer 12/22/2020

How does COVID-19 affect patients with hematologic malignancies? The ASH registry provides some answers 12/17/2020

How does COVID-19 affect patients with hematologic malignancies? The ASH registry provides some answers The ASH Research Collaborative COVID-19 Registry for Hematology was established earlier this year to study patients with hematologic malignancies diagnosed with COVID-19. Now, the registry also includes patients with nonmalignant hematologic disorders and hematologic manifestations of COVID-19. , of the University of North Carolina at Chapel Hill, recently presented data from the registry at the ASH Annual Meeting. In this episode, Dr. Wood tells host , how the registry came to be and reviews some of its findings. About the registry The registry is part of the ASH Research Collaborative, an organization established in 2018 to foster collaboration to accelerate progress in hematology. The registry houses data on patients with a COVID-19 diagnosis and hematologic disorders/malignancies or hematologic manifestations of COVID-19. Health care providers around the world can contribute data to the registry. Anyone can view summaries of the deidentified data on the registry website. The website data are updated every day or every few days. The information compiled in the registry includes: The nature of patients’ underlying disease Treatments received until COVID-19 diagnosis Sociodemographic information COVID-19 symptoms and time to resolution or death COVID-19–directed treatments Expected prognosis Whether patients opted for intensive care. Registry findings The registry data presented at ASH 2020 included 656 patients with hematologic malignancies and COVID-19. Dr. Wood said the first conclusion drawn from these data is that patients with underlying hematologic malignancies are a “medically vulnerable population” when it comes to COVID-19. The mortality rate was 20% overall and 33% in patients with hospitalization-level severity. The other major finding, Dr. Wood said, is that the risk of severe COVID-19 and death is differentially distributed. Risk factors for adverse COVID-19 outcomes include: Increasing age Advanced underlying disease or limited prognosis Forgoing intensive management. Relevant links ASH Research Collaborative: . COVID-19 Registry for Hematology: . Blood Adv. 2020. 4(23):5966-75. . Wood W et al. ASH 2020, Abstract 215. . Disclosures Dr. Wood disclosed research funding from Pfizer, consultancy for Teladoc/Best Doctors, and honoraria from the ASH Research Collaborative. Dr. Henry has no relevant disclosures. * * * For more MDedge Podcasts, go to Email the show: Interact with us on Twitter: David Henry on Twitter: /episode/index/show/jcsopodcast/id/17219870

News from ASH 2020: 'Practice-changing' results with ruxolitinib in chronic GVHD and no benefit seen with tranexamic acid in patients with blood cancers and severe thrombocytopenia 12/15/2020

How I treat GVHD: Dr. James Ferrara explains how biomarkers can predict outcomes and guide the treatment of acute GVHD 12/10/2020

How I treat GVHD: Dr. James Ferrara explains how biomarkers can predict outcomes and guide the treatment of acute GVHD A pair of biomarkers are being used to guide treatment and predict mortality in patients with graft-versus-host disease (GVHD), according to James L.M. Ferrara, MD, DSc, of the Icahn School of Medicine at Mount Sinai, New York. In this episode, explains how measuring these biomarkers – REG3-alpha and ST2 – can prevent over- and undertreatment of acute GVHD. The biomarkers have also been shown to predict nonrelapse mortality more accurately than a change in clinical symptoms. Before reviewing these findings, Dr. Ferrara tells host , what GVHD is, how to recognize it, and how it’s typically treated. GVL and GVHD GVHD is “very tightly associated” with the graft-versus-leukemia (GVL) effect, Dr. Ferrara explained. The GVL effect refers to the ability of donor immune cells to eliminate host malignant cells after allogeneic hematopoietic stem cell transplant (allo-HSCT). The donor T cells respond to minor histocompatibility antigens on malignant cells but also on normal cells. When the donor T cells attack the normal cells, the patient develops GVHD. To prevent GVHD, patients may receive cyclosporin, tacrolimus, methotrexate, sirolimus, or other drugs in various combinations. Despite prophylaxis, slightly under half of allo-HSCT recipients will still develop some form of GVHD, Dr. Ferrara said. Acute GVHD Acute GVHD typically occurs in the first month or two after transplant, and about 50% of cases happen in the first month, Dr. Ferrara said. There are three primary targets – the skin, liver, and GI tract. The rash observed with skin GVHD is vesiculopapular, and the extent of the rash determines the stage of GVHD in the skin. Increase in total bilirubin is used to measure the stages of liver disease. GVHD in the GI tract is characterized by persistent nausea and vomiting or diarrhea (up to liters a day). Evaluating the skin, liver, and GI tract together can provide the overall GVHD grade, between 1 and 4. Grade 4 GVHD is the most severe, and grade 1 is a skin rash that usually affects less than 50% of the body surface area. Over- and undertreatment When GVHD is mild and limited to the skin, topical steroid creams are adequate treatment. When GVHD progresses into the GI tract and liver, patients require systemic immunosuppression. However, it’s difficult to tell whether GVHD is going to be mild, moderate, or severe. So when patients with acute GVHD receive systemic steroids at a starting dose of 1 mg/kg, many of these patients are overtreated “and a fair number of them are undertreated because we don't actually know which patients are going to progress and which patients are going to respond to treatment,” Dr. Ferrara said. He noted that the JAK1/2 inhibitor ruxolitinib was approved to treat steroid-refractory acute GVHD last year. Prior to that, the only approved treatment for GVHD was systemic steroids. Biomarkers signal disease severity Through their research, Dr. Ferrara and colleagues identified two biomarkers of GVHD severity – REG3-alpha and ST2. “When the GI tract is damaged early, these proteins flood into the systemic circulation, and they can actually tell us who's got a damaged GI tract very early, even before one has symptoms like diarrhea,” Dr. Ferrara explained. The biomarkers can be used to assess, at the onset of GVHD, whether or not a patient has crypt damage and needs more intensive treatment. Biomarkers guide treatment, predict outcomes Dr. Ferrara and colleagues used serum samples collected by the Mount Sinai Acute GVHD International Consortium (MAGIC) to develop MAGIC Algorithm Probability (MAP). MAP is calculated from patients’ levels of REG3-alpha and ST2 and can be used to predict the risk of severe GVHD. “You put these two biomarkers into an equation, you get a single number, and that number tells you whether [the patient is] high risk, low risk, or intermediate risk,” Dr. Ferrara explained. He and his colleagues found they could use MAP to predict patients’ response to treatment and mortality. In fact, MAP was able to predict nonrelapse mortality more accurately than a change in clinical symptoms (Blood Adv. 2019. 3[23]:4034-42. ). Standard practice, ongoing trials MAP is increasingly becoming a part of standard practice, Dr. Ferrara said. A company called Viracor Eurofins Clinical Diagnostics licensed MAP and provides tests for consumer use (). Centers can send blood samples to Viracor to test. More than 50 centers in the United States sent at least 1,000 samples to Viracor for testing in 2019, Dr. Ferrara said. He and his colleagues are also utilizing MAP in ongoing clinical trials: A phase 2 study of natalizumab plus standard steroid treatment for high-risk acute GVHD (NCT02133924; ). A pilot trial of alpha1-antitrypsin for preemption of steroid-refractory acute GVHD (NCT03459040; ). A phase 2 trial of itacitinib for low-risk GVHD (NCT03846479; ). Disclosures: Dr. Ferrara has a patent for serum biomarkers of acute GVHD and receives royalties from Viracor. Dr. Henry has no relevant disclosures. * * * For more MDedge Podcasts, go to Email the show: Interact with us on Twitter: David Henry on Twitter: /episode/index/show/jcsopodcast/id/17115761

Black patients with ES-SCLC get less chemo, CTCs may guide breast cancer treatment, and new FDA approvals for neuroblastoma and prostate cancer 12/08/2020

Can aerosolized chemotherapy better treat peritoneal carcinomatosis in patients with gynecologic or gastrointestinal cancers? 12/03/2020

Can aerosolized chemotherapy better treat peritoneal carcinomatosis in patients with gynecologic or gastrointestinal cancers? Researchers are conducting the first U.S. trial of pressurized intraperitoneal aerosolized chemotherapy (PIPAC) for the treatment of peritoneal carcinomatosis in patients with gynecologic or gastrointestinal cancers. Coprincipal investigator , of City of Hope in Duarte, Calif., describes this trial and the PIPAC procedure to host , in this episode. To start, the pair discuss a patient who might be eligible for PIPAC – one with stage 3 ovarian cancer. General approach to stage 3 ovarian cancer Therapy typically includes a combination of surgery and chemotherapy. The order in which chemotherapy is given, either pre- or postoperatively, depends on performance status and whether patients have extra-abdominal disease or parenchymal liver disease. Operative approaches, including debulking surgery, are pursued if believed to be optimal, meaning all gross residual disease can be resected. If all residual disease cannot be resected, patients are offered neoadjuvant chemotherapy, typically for three to four cycles before an interval debulking surgery, followed by postoperative adjuvant chemotherapy. Intraperitoneal chemotherapy Intraperitoneal (IP) chemotherapy is used to treat peritoneal surface malignancies. The peritoneum is a separate organ that is difficult to treat adequately with intravenous chemotherapy alone. Giving IP chemotherapy in combination with intravenous chemotherapy may be more effective than intravenous chemotherapy alone (N Engl J Med. 2006; 354:34-43; ). However, there are many challenges in delivering IP chemotherapy, including increased side effects of abdominal pain and IP catheter failure. Recent clinical trials have shown that, with the addition of bevacizumab, the survival benefit with IP chemotherapy may not be as significant as prior trials suggested (J Clin Oncol. 2019 Jun 1;37[16]:1380-90; ). In general, IP chemotherapy has not been embraced by the medical oncology community as much other types of chemotherapies, Dr. Dellinger said. What is PIPAC? PIPAC is a novel therapy discovered by a German surgical oncologist, Marc A. Reymond, MD, from University of Tuebingen (Germany). PIPAC delivers chemotherapy at a reduced dose directly into the intraperitoneal cavity but in a pressurized and aerosolized form. PIPAC is done at the time of the diagnostic laparoscopy and requires a nebulizer for aerosolization of the chemotherapy as well as a high-pressure injector. This approach allows for the chemotherapy to be pushed deeper into tissues, compared with hyperthermic intraoperative peritoneal chemotherapy (HIPEC). With HIPAC, tissue penetration is typically 1 mm or less. With PIPAC, there is deeper penetration and better distribution of chemotherapy throughout the entire intraperitoneal cavity. With PIPAC, chemotherapeutic agents are given at a lower dose than is typically administered with IP or intravenous chemotherapy, which helps in reducing the toxicity. PIPAC is given every 6 weeks for three cycles, requiring three laparoscopic procedures. These laparoscopic procedures allow for the opportunity to obtain peritoneal tumor biopsies before and after to investigate the natural course of these tumors and their microenvironment. Toxicity of PIPAC PIPAC has been done in more than 800 patients with gastrointestinal and gynecologic cancers in Europe and Asia. Severe adverse events have been minimal, with about 12%-15% grade 3/4 SAEs and very rare grade 5 SAEs. The most common side effect is typically abdominal pain, attributed to the IP administration in conjunction with the laparoscopic surgery. Renal toxicity is a concern with intravenous cisplatin use, but this has not yet been seen with PIPAC. With PIPAC, cisplatin is given at 10.1 mg/m2 and doxorubicin is given at 2.1 mg/m2, doses that are much lower than the typical doses for these drugs. PIPAC in clinical trials PIPAC clinical trials have moved into phase 2 in Europe for ovarian cancer, with a publication demonstrating an objective response rate of over 60% in platinum-resistant ovarian cancer (Gynecol Oncol. 2015 May;137[2]:223-8; ). A phase 3 trial of PIPAC was planned but was stalled because of the COVID-19 pandemic. Because of the need for Food and Drug Administration approval, researchers have just launched the first phase 1 trial of PIPAC in the United States. Phase 1 trial of PIPAC City of Hope is working with affiliates at Mayo Clinic in Jacksonville, Fla.; Northwell Health in New York; and the National Institutes of Health to enroll eligible candidates for a phase 1 trial (NCT04329494; ). Eligible candidates include those with gastric, uterine, colorectal, appendiceal, and ovarian cancer with evidence of peritoneal carcinomatosis who have failed at least one line of therapy. PIPAC is an outpatient procedure, but given the trial and need for monitoring, patients typically leave the hospital the following day after blood samples are obtained for the study. City of Hope has recruited seven patients since activating their study in August 2020, with a goal of enrolling 16 patients by spring 2021. Future directions Peritoneal tumor biopsies obtained during the laparoscopic procedures are being used to study the microenvironment of these cancers. In eventual phase 2 clinical trials, the researchers may include immune checkpoint inhibitors. Biomarker analyses are underway, looking at expression of PD-1 and tumor-infiltrating lymphocytes. The researchers are also studying the role of genomic sequencing and DNA repair. Disclosures: Dr. Dellinger and Dr. Henry have no financial disclosures relevant to this episode. Show notes by Sheila De Young, DO, resident at Pennsylvania Hospital, Philadelphia. * * * For more MDedge Podcasts, go to Email the show: Interact with us on Twitter: David Henry on Twitter: /episode/index/show/jcsopodcast/id/17011697

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