In this video, Dr. Matthew Davids, M.D., an Associate Professor of Medicine at Harvard Medical School and the Director of Clinical Research for Lymphoma at Dana-Farber Cancer Institute in Boston, is interviewed by CLL Society founder and Chief Medical Officer, Dr. Brian Koffman, M.D., a retired family physician and a CLL patient. This video was recorded at the 62nd Annual Meeting of the American Society of Hematology, held virtually in December 2020. Dr. Davids specializes in CLL and serves on the CLL Society’s Medical Advisory Board.
The MURANO study showed that venetoclax (Venclexta®) plus rituximab is an effective time-limited regimen for treating patients with relapsed or refractory (R/R) CLL. This regimen’s two potential drawbacks are that it is a two-year treatment period, and rituximab is a product infused intravenously, requiring numerous visits to an infusion clinic.
The team at Dana-Farber felt that the combination of duvelisib (Copiktra™) and venetoclax (Venclexta®) would lead to deep remissions that would allow for oral only therapy of one-year duration. The options for reaching deep remissions in R/R CLL are limited, so this could represent a future additional option in the CLL physician’s toolbox.
Take-Aways
- This trial enrolled 22 patients as of the study data cutoff date of July 19, 2020. The median patient age was 69 (range, 50-78). Patients in this group had high-risk genomics, including deletion(17p) 7/22 (32%), TP53 mutation 10/22 (45%), deletion (11q) 2/22 (9%), unmutated IGHV 20/22 (91%) and mutation in NOTCH1 10/22 (45%). The median number of prior treatments for this group was 3 (range, 1-6), including two patients who relapse after stem cell transplant and 15/22 (68%) previously treated with a BTK, such as ibrutinib or acalabrutinib. Of those who had prior BTK exposure, seven had progressed on that therapy.
- Hematologic side effects were the most common. Neutropenia or low neutrophil counts occurred in 78% of participants. Of those who developed neutropenia, 68% were the more severe grade 3 or higher. Seventy percent of patients who developed neutropenia required some form of active management such as administration of the growth-factor drugs filgrastim or pegfilgrastim.
- The immune-mediated side effects associated with the PI3k class of drugs only occurred in three patients, each experiencing diarrhea, colitis, and liver inflammation.
- Eleven patients held duvelisib treatment temporarily; nine patients had a duvelisib dose reduction, and six discontinued duvelisib due to toxicity issues.
- The median number of cycles was 7.5 (range, 1-22). The overall response rate (ORR) for CLL / SLL was 94% (17/18). 56% of patients attained complete response (CR), and 39% reached partial response. The one patient not counted in the ORR elected to undergo a stem cell transplant before an assessment of response occurred.
- As of the data cutoff, 56% (10/18) achieved undetectable minimal residual disease (uMRD). Four patients had not reached the point of evaluation. Of the patients who have completed 1-year duvelisib and venetoclax, 58% (7/12) had a CR with uMRD and stopped all treatment. This group included two deletion (17p) patients.
Conclusions:
Duvelisib plus venetoclax was shown to be active in patients with R/R CLL / SLL. The side effects are consistent with those associated with the individual drugs.
At present, there are approved standard of care venetoclax-based options available, making this combination of interest for patients interested in oral-only treatments of fixed duration.
Follow-up data on this trial is ongoing, and we look forward to more data in the future.
The link to find out where this Phase I/II clinical trial is available and more information is: https://clinicaltrials.gov/ct2/show/NCT03534323
To learn more about clinical trials, in general, go to https://cllsociety.org/clinical-trials
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 E. Henry III 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 as a licensed pharmacist and has served as Chief Pharmacy Officer at two Top-15 Comprehensive Cancer Centers, Moffitt (Tampa, FL) and Roswell Park Cancer Institute (Buffalo, NY).
