EHA 2019: Dr Matthew Davids on Combination Therapies with Chemotherapy

In this video, Dr. Brian Koffman, MDCM, a CLL patient, family physician and Chief Medical Officer of the CLL Society, interviews Dr. Matthew Davids, MD, MMSc, Associate Director – Center for Chronic Lymphocytic Leukemia at Dana-Farber Cancer Institute (DFCI) and Assistant Professor of Medicine, at Harvard University. This interview occurred at the European Hematology Association (EHA) Congress, in Amsterdam, Netherlands, earlier this year.

Dr. Davids discusses a clinical trial using combination therapies he leads at DFCI, that addresses younger and fitter patients, with limited or no co-morbidities. Patients over 65 are excluded from this trial because they likely could not tolerate the “gold standard” chemotherapy/immunotherapy regimen, fludarabine, cyclophosphamide and rituximab (FCR).  Dr. Davids believes that older patients can still benefit from combination therapies involving non-chemo novel agent/novel agent (such as ibrutinib + venetoclax); novel agent/CD 20 monoclonal antibody (such as venetoclax + obinituzimab) or by sequencing novel agents.

Traditionally, patients receive FCR for up to 6 months (generally receiving less if tolerance issues arise).  About 50 to 55-percent of patients who have mutated immunoglobulin heavy chain region genes (IGHV) and receive FCR obtain remissions lasting for extended periods of time often 12-15 years.  However, patients with unmutated IGHV don’t seem to get the same extended term response as the mutated group sees.

In this trial, Dr. Davids is looking at combining FCR with Ibrutinib. In this regimen patients receive FCR plus ibrutinib for 6-months and then continue on ibrutinib for two years.  Interestingly, the response deepens during the ibrutinib monotherapy. This trial initially involved 35 patients of whom 4 were 17p deleted. The trial was subsequently expanded to 85 patients, and because the 17p patients at best obtained partial response none were included in the second cohort. Amazingly, the combination resulted in 84 percent of patients having undetectable minimal residual disease (uMRD) with the combination and there was no difference between the mutated and unmutated groups.  Patients will now be observed to determine of uMRD translates into durable response beyond FCR alone.  The combination therapy saw no greater adverse reactions than would be expected with the individual treatments.

There is some vigorous debate in CLL circles these days as to whether there is still a place for chemo-immunotherapy in treating CLL.  Dr. Davids believes that there is and that the addition of ibrutinib may improve outcomes further.

Here is Dr. Koffman’s interview with Dr. Davids at EHA, 2019:

Here is the EHA abstract: IBRUTINIB PLUS FLUDARABINE, CYCLOPHOSPHAMIDE, AND RITUXIMAB (IFCR) AS INITIAL THERAPY FOR YOUNGER PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA: A SINGLE-ARM, MULTICENTER, PHASE 2 TRIAL

Tom Henry

Clinical Pharmacy Advisor, Lumere
President and Senior Consultant, Burlington Consulting Associates
Has served as Chief Pharmacy Officer at two Top-15 Comprehensive Cancer Centers, Moffitt (Tampa, FL) and Roswell Park, (Buffalo, NY)