Matthew S. Davids, MD, MMSc, Discusses Rationale for the MAJIC Study of Venetoclax Plus Acalabrutinib in CLL

Matthew S. Davids, MD, MMSc, spoke about using venetoclax plus acalabrutinib in the phase 3 MAJIC study for patients with chronic lymphocytic leukemia or small lymphocytic lymphoma.

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 the phase 3 MAJIC (NCT05057494) trial utilizing venetoclax (Venclexta) and either acalabrutinib (Calquence) or obinutuzumab (Gazyva) in patients with previously untreated chronic lymphocytic leukemia or small lymphocytic lymphoma.


We’re fortunate now in CLL that we have several very active novel agents. We have strategies that include continuous BTK [Brutons tyrosine kinase] inhibitor therapies and then we have strategies that include time-limited therapy in the frontline setting with the venetoclax plus obinutuzumab regimen. In the future, we’re going to be looking more at time-limited therapies in CLL because it allows for shorter duration of therapy. That means fewer [adverse] effects, less cost, and hopefully a better lifestyle for patients who don’t need to be continuously reminded that they’re taking cancer pills.

The idea with the MAJIC study is to look at the newer, more-specific BTK inhibitor acalabrutinib in combination with venetoclax. That’s the experimental arm that’s been compared to the more standard regimen of venetoclax plus obinutuzumab. It’s a randomized phase 3 trial to help define what the optimal combination partner is for venetoclax in the frontline setting. Is it a BTK inhibitor or is it obinutuzumab?

The study will [include] about 750 patients recruited and randomized 1:1 to these 2 arms. The unique aspect of the study is that the duration of therapy in both arms is guided by minimal residual disease. It could be 1 or 2 years of venetoclax therapy in either arm. We’re hoping that that will help to minimize the amount of therapy needed for patients who have more sensitive disease, but to potentially extend therapy for those patients who have more resistant disease and need a longer course.

We’re aiming to open the MAJIC study in the first quarter of 2022, so it’s coming soon. It’s a global study, so it’ll be open here in the United States, but also outside of the US at about 40 sites. There’s been a lot of enthusiasm for the study, so we hope that it will accrue quickly.


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

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