In this video, Dr. Meghan C Thompson, MD, a second-year fellow in the CLL Program at Memorial Sloan Kettering Comprehensive Cancer Center, in New York City, is interviewed by CLL Society, co-founder and Chief Medical Officer, Dr. Brian Koffman, MD, a retired family physician and a CLL patient. This video was recorded at the 62nd Annual Meeting of the American Society of Hematology in December 2020 in a virtual format.
There have been many advances in Chronic Lymphocytic Leukemia (CLL) treatment over the past decade. Historically, many of the therapies available to treat CLL were used sequentially in that patients would remain on one therapy until either they experienced disease progression or the adverse effects of toxicities precluded continued use. Venetoclax (Venclexta®) has revolutionized CLL treatment in that it is used more today in fixed-duration combination regimens. The CLL14 trial (venetoclax + obinutuzumab) and the MURANO trial (venetoclax + rituximab) led to the approval of fixed duration treatments in treatment naïve and relapsed/refractory patients, respectively. Fixed-duration venetoclax-based regimens are now considered the standard of care (SOC).
Despite very high overall response rates with these fixed-duration venetoclax-based combinations, some patients do relapse over time. Because the reason for the discontinuation of venetoclax was because of the end of planned treatment, and not because the CLL had become resistant, clinicians have asked the question, “Can we retreat with venetoclax?” Until recently, there was no data to support the second use of a venetoclax based regimen. Dr. Thompson’s poster presentation points to the need for further study and potentially a prospective clinical trial.
- Investigators conducted a multicenter retrospective study of CLL patients treated with a venetoclax (Ven)-based regimen (Ven1) and then retreated with a second Ven-based regimen in a subsequent line of therapy (LOT).
- Researches analyzed patient records from 13 centers and the CLL Collaborative Study of Real-World Evidence database.
- The study identified 25 patients who were re-treated with venetoclax.
- The median prior lines of therapy among this group was 2 (range, 0-10).
- Sixty (60) percent of the study subjects had received a Bruton’s Tyrosine Kinase (BTK) inhibitor such as ibrutinib or acalabrutinib in the past.
- This study’s subjects had a median exposure to Ven1 of 15 months and an overall response rate (ORR) of 88%. Moreover, eight (8) patients (80%) achieved undetectable Measurable Residual Disease (MRD) by flow cytometry at the level of less than one cell in 10,000.
- The median time between Ven1 and Ven2 was 8.7 months. Eighty-Eight (88) percent of patients had no other treatment between Ven1 and Ven2.
- No patients experienced Tumor Lysis Syndrome at the clinical level; however, 4.5% of patients had electrolyte elevations or “lab TLS.”
- The ORR to Ven2 treatment was 72.2%.
This study’s 25 subjects appear to be the largest cohort of patients evaluated after retreatment with venetoclax.
The high ORR suggests that retreatment is a promising strategy, and clinicians should consider it in treatment sequencing decisions.
Further study, including prospective clinical trials, appear to be warranted.
Please enjoy Dr. Koffman’s interview with Dr. Thompson: ASH 2020: Dr. Meghan Thompson MD Venetoclax Retreatment that goes into even more detail.
Here is her actual abstract: Venetoclax Re-Treatment of Chronic Lymphocytic Leukemia (CLL) Patients after a Previous Venetoclax-Based Regimen.
Thanks for reading and viewing this interview.
Stay strong; we are all in this together.
Thomas. E. Henry III, MBA, RPh, CPh
Thomas Henry is a Registered Pharmacist and CLL Patient. He is President and Senior Consultant for Burlington Consulting Associates, a company that provides consulting services to health systems nationwide. Tom is a CLL Society Medical Advisory Board member and strives to educate other CLL patients through his blog https//www.cllpharmacist.com. He has a forty-two-year career in pharmacy and has served as Chief Pharmacy Officer at two Top-15 Comprehensive Cancer Centers, Moffitt (Tampa, FL) and Roswell Park (Buffalo, NY).