How I treat CLL and MCL: From ‘watch and wait’ to BCL2 and BTK inhibitors, CAR T-cell therapy, and transplant
Release Date: 03/11/2021
Biosimilars with Dr. Gary Lyman
Blood & Cancer
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...
info_outline
Advanced bladder cancer: Dr. Arjun Balar talks treatment strategies in a changing field
Blood & Cancer
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...
info_outline
Gene therapies in hemophilia with Dr. Glenn Pierce
Blood & Cancer
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...
info_outline
Thrombosis and thrombocytopenia caused by COVID-19 vaccines: How to identify and treat VITT, VIPIT, or TTS
Blood & Cancer
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)...
info_outline
Toward more personalized treatment in prostate cancer: The CCR score predicts metastasis and guides treatment decisions after radiation
Blood & Cancer
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...
info_outline
Changing perspectives: Dr. Michael Weiner recounts his experiences as an oncologist who became a cancer patient and then a caregiver
Blood & Cancer
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....
info_outline
Optimizing CAR T-cell therapies in lymphoma: Improving response, fighting cytokine release syndrome, and identifying mechanisms of resistance
Blood & Cancer
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...
info_outline
Trends in genetic testing for breast and ovarian cancer: Undertesting and racial/ethnic disparities persist
Blood & Cancer
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...
info_outline
Improving cancer screening in the COVID era: Drive By Flu-FIT allows for socially distanced colorectal cancer screening
Blood & Cancer
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...
info_outline
Unpacking von Willebrand disease guidelines: Dr. Paula James talks diagnosis and pre-procedure prophylaxis
Blood & Cancer
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...
info_outlineTreatments for chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL) have advanced in recent years, with more new developments on the horizon.
James Gerson, MD, of the University of Pennsylvania, Philadelphia, reviewed some of these advances and future directions while describing how he would treat three patients. Host David H. Henry, MD, 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. https://bit.ly/38pVHbf).
- 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 (https://bit.ly/38onIjy).
- 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. https://bit.ly/3rvRv1h).
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 mdedge.com/podcasts
Email the show: [email protected]
Interact with us on Twitter: @MDedgehemonc
David Henry on Twitter: @davidhenrymd