Matthew Steven Davids, MD, MMSc, Discusses a Phase II Study for Richter’s Syndrome

As of the data cut on February 3, 2020, the study – presented at the 2020 American Society of Clinical Oncology (ASCO) Virtual Scientific Program – suggested the treatment combination may be effective in this patient population.

The study enrolled 27 patients. Notably, 6 patients were not evaluable for efficacy of the combination (5 had toxicity in cycle 1 and never started venetoclax, 1 withdrew after cycle 1).

Of the 21 patients who started combination therapy, the overall response rate (ORR) was 76% and the complete response (CR) rate 62%. Only 1 patient with a CR has progressed.

The patient who has remained on venetoclax maintenance the longest is in CR for 2 years post-chemotherapy. Further, 8 patients went to allogeneic hematopoietic cell transplantation (allo-HCT), with patients still in CR now up to 2.5 years post-allo-HCT. With a median follow-up of 9.3 months (range 0.6-30), the median progression-free survival (PFS) and overall survival (OS) are both 16.3 months.

Matthew Steven Davids, MD, MMSc, an attending physician in the Lymphoma Program of the Division of Hematologic Malignancies and associate director of the CLL Center at the Dana-Farber Cancer Institute, spoke with CancerNetwork® about the study and the planned next steps for this patient population.

Transcription:

So in terms of the results so far, we've seen really excellent efficacy from this regimen. For the evaluable patients who received the combination, about two thirds have achieved complete remission. And when we compare that back to the historical results that we would get with R-EPOCH alone, that's only about a 20% rate. So it does seem like there's some distinction there and a pretty compelling rate of complete remission.

All the patients who had bone marrows checked also had undetectable MRD for CLL. So it does seem to be very effectively controlling the CLL. And many of these were very high risk patients who needed to move along to allo-transplant to have a hope of long term survival. And about half of the patients who are candidates to move on to allo-transplant, were able to do that, which again is higher than we might expect from the chemotherapy alone.

So whereas historically, you know this is a very high risk group, where we see median overall survival in the range of only three to six months, so far, in our study, we've seen a median overall survival of 16.3 months. So this is not a controlled study. It's a single arm study, but we certainly think these look like promising results compared to the historical results we'd expect from chemo alone. We certainly did see some toxicity with this regimen, in particular cytopenias, neutropenia, and thrombocytopenia. And we saw some significant infectious complications as well, including sepsis, as well as febrile neutropenia

So moving forward in terms of the the next steps for this study, we've decided to open an expansion cohort. And in this cohort, we're going to change the chemotherapy backbone and use R-CHOP instead of R-EPOCH. We're hoping that the R-CHOP will be less myelo-suppressive and lead to fewer infections. But we're continuing the venetoclax with the same schedule, thereby hopefully preserving this chemosensitization strategy. And so we're very eager to to explore this new regimen to see if we can build on the results of this initial study.

Reference:

Davids MS, Rogers KA, Tyekucheva S, et al. A multicenter phase II study of venetoclax plus dose-adjusted R-EPOCH (VR-EPOCH) for Richter’s syndrome.