Dr Brown on Important Clinical Trials to Watch for in CLL

“[MAJIC] is going to give us insight relative to how we would use these 2 different regimens.”

Jennifer R. Brown, MD, PhD, director of the CLL Center of the Division of Hematologic Malignancies at Dana-Farber Cancer Institute and the Worthington and Margaret Collette Professor of Medicine in the Field of Hematologic Oncology at Harvard Medical School, discussed multiple ongoing clinical trials evaluating BTK inhibitors and BCL-2 inhibitors for the management of chronic lymphocytic leukemia (CLL) and how they relate to the February 2026 FDA approval of acalabrutinib (Calquence) plus venetoclax (Venclexta) for CLL and small lymphocytic lymphoma.

The approval was based on data from the phase 3 AMPLIFY trial (NCT03836261), which showed that patients who received acalabrutinib plus venetoclax (n = 291) achieved a 3-year progression-free survival (PFS) rate of 76.5% (95% CI, 71.0%-81.1%) vs 66.5% (95% CI, 59.8%-72.3%) in the standard-of-care chemoimmunotherapy arm (n = 290). The 3-year overall survival rates in each arm were 94.1% (95% CI, 90.7%-96.3%) and 85.9% (95% CI, 81.0%-89.6%), respectively.

Despite the promising efficacy of the combination, Brown pointed out how alternative evaluations of acalabrutinib plus venetoclax in CLL might provide useful insight. She specifically highlighted the phase 3 MAJIC trial (NCT05057494), which is evaluating the combination with a time-based minimal residual disease (MRD) end point. In the trial, patients receiving the combination will be evaluated after 12 cycles of treatment for undetectable MRD. If patients have undetectable MRD, they will discontinue treatment. If they have detectable MRD, they will continue treatment for another 12 cycles, she added. Brown also mentioned that in the trial, the combination will be compared with a comparator regimen containing the same combination but with the addition of obinutuzumab (Gazyva). The trial will provide data about the likelihood of undetectable MRD at 1 year for the combination and whether a second year of treatment affects PFS rates, she said.

Brown concluded with a conversation about alternative BTK and BCL-2 inhibitors like zanubrutinib (Brukinsa) and sonrotoclax (BGB-11417), underscoring how the combination of these 2 agents has shown promise regarding undetectable MRD. Brown noted that she is looking forward to seeing how the undetectable MRD rates of each combination stack up against one another.