Matthew S. Davids, MD, MMSc, Discusses Extended Use of Venetoclax in CLL

At the 2021 American Society of Hematology Annual Meeting, CancerNetwork® spoke with Matthew S. Davids, MD, MMSc, an associate professor of medicine at Harvard Medical School and director of Clinical Research in the Division of Lymphoma at Dana-Farber Cancer Institute, about why it was important to increase venetoclax (Venclexta) usage from 12 to 24 months in time-limited therapy regimens for chronic lymphocytic leukemia (CLL). He discussed several treatment benefit that, hopefully, may result in lasting remission in patients with previously untreated chronic lymphocytic leukemia or small lymphocytic lymphoma.

Notably, Davids discussed this strategy in context of the phase 3 MAJIC (NCT05057494) trial, in which patients with previously untreated CLL are randomized to therapy with venetoclax plus either acalabrutinib (Calquence) or Obinutuzumab (Gazyva).

Transcript:

We think that time-limited therapy discontinuing [venetoclax] at 24 months will be advantageous for several reasons. Some of these include minimizing toxicity and reducing cost, but there may also be certain scientific reasons as well. We know that if we expose cancer cells to a particular therapy over a long period of time, in many cases, eventually the cancer cells will develop resistance, [such as] resistance mutations or other functional mechanisms that will make the therapy no longer effective.

The idea of that hypothesis is that if we give a very active time-limited regimen for a short period of time, 1 year or 2 years, we can get patients into very deep remissions with high rates of undetectable minimal residual disease [MRD], and that this will provide a durable benefit without the need for ongoing treatment. The hope would be then if the patient did relapse later that they could potentially even be retreated with the same regimen and that their cancer would still be sensitive to that treatment. That’s the rationale. In the MAJIC study, one of the unique aspects is that it is an MRD-guided strategy for both arms. Even [with] venetoclax plus obinutuzumab—which is approved as a 1-year regimen—and essentially all other studies that are underway right now in CLL, the phase 3 studies are using a fixed-duration of 1 year. Our study is unique and that you can get a second year of venetoclax in that arm of the study to really make it more equivalent to the 2 years of acalabrutinib [Calquence] and venetoclax and the other arm.

Reference

Davids M, Mato A, Hum J, et al. Majic: a phase 3 prospective, multicenter, randomized, open-label trial of acalabrutinib plus venetoclax versus venetoclax plus obinutuzumab in previously untreated chronic lymphocytic leukemia or small lymphocytic lymphoma. Blood. 2021;138(suppl 1):1553. doi:10.1182/blood-2021-148155