Three-Drug Combination Therapy May Be Effective in Patients With High-Risk CLL

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A three-drug combination that showed success at sending patients with chronic lymphocytic leukemia (CLL) into deep remissions in a clinical trial may be effective at treating patients with high-risk types of the disease, according to new findings presented by Ryan et al at the 2022 American Society of Hematology (ASH) Annual Meeting and Exposition (Abstract 344).

Study Methods and Results

The initial cohort of the trial—which included patients with any subtype of CLL—found that a regimen of acalabrutinib, venetoclax, and obinutuzumab produced deep remissions in 89% of participants. In the new phase II clinical trial, which exclusively included patients with high-risk CLL, researchers discovered that the same drug combination resulted in a similar deep-remission rate of 83%.

The trial involved 68 patients with previously untreated CLL, 41 of whom had a mutation and/or deletion in the TP53 gene in their tumor cells. The patients were treated with acalabrutinib, obinutuzumab, and venetoclax on a specified schedule that they could continue for up to 16 cycles.

At a median follow-up of 35 months, 83% of the patients with high-risk CLL had undetectable minimal residual disease in their bone marrow, and 45% of them had the deepest measurable response to the treatment: complete remission and undetectable minimal residual disease in their bone marrow.

Overall, the researchers found that the patients tolerated the treatment well—with low rates of cardiovascular complications and infections. After nearly 3 years of follow-up, there was a progression-free survival rate of 93% among the trial participants.


The study has in part supported the development of a large, phase III trial of the three-drug regimen for patients with CLL without high-risk disease, and may have the potential to lead to U.S. Food and Drug Administration (FDA) approval of the regimen.

“Our data provide foundational support for using this triplet therapy in patients with high-risk CLL,” concluded senior study author and principal investigator Matthew S. Davids, MD, MMSc, Associate Professor of Medicine in the Department of Medical Oncology and Director of Clinical Research in the Division of Lymphoma at the Dana-Farber Cancer Institute.

Disclosure: The research in this study was supported by AstraZeneca and an award from the National Institutes of Health. For full disclosures of the study authors, visit

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