In this video, Professor Constantine Tam, MD, Director of Haematology and Lead of the Chronic Lymphocytic Leukemia (CLL) and Low-Grade Lymphoma Program at Peter MacCallum Cancer Centre in Melbourne, Australia, is interviewed by CLL Society co-founder and Chief Medical Officer, Dr. Brian Koffman, MDCM, a retired family physician and a CLL patient. This video was recorded at the 61st Annual Meeting of the American Society of Hematology in 2019, in Orlando, Florida.
In this interview, Dr. Tam, who is the lead investigator of the Captivate Trial, discusses the most recent results of this trial. Dr. Tam’s presentation is more fully explained in the monograph Ibrutinib (Ibr) Plus Venetoclax (Ven) for First-Line Treatment of Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL): Results from the MRD cohort of the Phase 2 CAPTIVATE study.
This phase of the study included 164 patients who received the combination of ibrutinib (Imbruvica®) and venetoclax (Venclexta®) as front-line treatment for CLL/SLL. Patients received three (3) months of ibrutinib 420mg once a day, followed by 12 months of ibrutinib 420mg + venetoclax. For this study the venetoclax followed the recommended weekly ramp-up dosing with doses of 20mg per day x 7 days, 50mg per day x 7 days, 100mg per day x 7 days, 200mg per day x 7 days and then the full dose of 400mg per day for the remaining 11 cycles. Of the original cadre of 164 patients, 151 were able to complete the full 15 cycles. This group included significant numbers of high-risk patients (16% were 17p deletion; 20% had either 17p or TP53 mutation; 16% had 11q deletion without 17p; 19% had complex karyotype, and 59% had unmutated IGHV).
The exciting news is at some point within the trial, 75% of patients reached undetectable Minimal Residual Disease (uMRD) in the blood, and 72% reached uMRD in the bone marrow. The term uMRD is when a lab is not able to find a single cancer cell when looking at a sample of 10,000 lymphocytes. Some very new and more sensitive tests can determine if there are any cancer cells in a sample of 1,000,000 lymphocytes.
The results of this trial are exciting! So exciting that I asked Dr. Javier Panilla, MD, my CLL specialist at Moffitt Cancer Center here in Tampa, if we could emulate this study. He agreed, and so did my insurance, so I am now just starting month four of the combination after being on ibrutinib for 46 months.
We know that, as of today, there is no cure for CLL. Ibrutinib, which was the first targeted therapy approved for CLL, merely controlled the progression of the disease and required continuous medication for life, or until progression of the CLL, or the side effects were not tolerable/manageable.
The Captivate Trial continues to determine if it is possible to have a time-limited treatment and that if uMRD is reached, could patients come off medication at least temporarily. Time-limited treatment would allow the patient a drug holiday where they would return to active observation, which is also known as “watch and wait.” After a drug holiday, researchers believe patients could return to ibrutinib and venetoclax, or just ibrutinib or just ventoclax, if needed, with no loss of efficacy. We will all be looking forward to additional updates on this study.
Thanks for reading this summary 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 provide consulting services to health-systems nationwide. He has a forty 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).
Originally published in The CLL Society Tribune MRD Special Edition.