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ASH 2025 | Mutation-guided finite-duration AV after first-line BTKi+ven-based therapy in CLL/SLL: MAVRiC trial
Matthew Davids, MD, Dana-Farber Cancer Institute, Boston, MA, provides insight into the MAVRiC trial (NCT07024706), an upcoming Phase II trial that will investigate the efficacy of retreatment with acalabrutinib plus venetoclax (AV) in patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) who have relapsed after first-line finite-duration therapy with a BTK inhibitor (BTKi) plus venetoclax (ven)-based combination. Dr Davids highlights that the study’s unique aspect is the use of IGHV mutational status to determine therapy duration. This interview took place at the 67th ASH Annual Meeting and Exposition, held in Orlando, FL.
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Transcript
So one of the key questions in the field of CLL now is after initial frontline fixed-duration or MRD-guided time-limited therapy, can you retreat patients successfully with a similar mechanism? And so that’s what the MAVRiC study is going to focus on. This is actually a trials-in-progress poster here to really just outline what the study design is. And in our study, we’re taking patients who were previously treated with a BTK plus BCL2 combination in the frontline therapy...
So one of the key questions in the field of CLL now is after initial frontline fixed-duration or MRD-guided time-limited therapy, can you retreat patients successfully with a similar mechanism? And so that’s what the MAVRiC study is going to focus on. This is actually a trials-in-progress poster here to really just outline what the study design is. And in our study, we’re taking patients who were previously treated with a BTK plus BCL2 combination in the frontline therapy. It doesn’t matter which BTK or BCL2 inhibitor, doublet or triplet therapy with obinutuzumab. And then on our study, we’re going to treat these patients with a doublet of acalabrutinib plus venetoclax.
One of the unique aspects of our study is that the duration of therapy is based on their IGHV mutational status. So not MRD, but IGHV mutational status, which you’ll know going into the study. And the hypothesis here is that patients with unmutated IGHV probably will require, in general, longer treatment since they have more active disease kinetics. So those patients get two years of therapy. Whereas patients with mutated IGHV who generally have a more indolent CLL will get one year of therapy, which we hope will be enough to get them into a meaningfully long remission. So this is a global multicenter study planned for about 80 patients that should be opening in early 2026 around the world. And we highly encourage people to consider enrolling their patients.
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