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Jeremy S. Abramson, MD, MMSc
Jeremy S. Abramson, MD, MMSc
Posted: Tuesday, January 21, 2025
Matthew S. Davids, MD, MMSc, of Dana-Farber Cancer Institute, Boston, and colleagues conducted the phase III AMPLIFY study to evaluate the combination of fixed-duration acalabrutinib, venetoclax, and obinutuzumab in patients with treatment-naive chronic lymphocytic leukemia (CLL). Results from the updated primary efficacy analysis, which included patients with TP53-aberrant CLL, were presented during the 2024 American Society of Hematology (ASH) Annual Meeting & Exposition (Abstract 1865). Acalabrutinib is a Bruton’s tyrosine kinase inhibitor, venetoclax is a BCL2 inhibitor, and obinutuzumab is a monoclonal antibody.
“In patients with TP53-aberrant CLL, the acalabrutinib, venetoclax, and obinutuzumab triplet is a well-tolerated and highly active measurable residual disease [MRD]-guided front-line therapy, with 71% of patients achieving peripheral blood- and bone marrow–undetectable MRD at cycle 16,” the authors concluded. “Our data support further study of acalabrutinib, venetoclax, and obinutuzumab for patients with treatment-naive high-risk CLL in [future] trials.”
A total of 72 patients with treatment-naive CLL were enrolled into cohort 1, and 35 patients with TP53-aberrant CLL were enrolled into the multicenter expansion. Participants received one 28-day cycle of twice-daily acalabrutinib, followed by two cycles of acalabrutinib, venetoclax, and obinutuzumab. If bone marrow–undetectable MRD with a complete response was achieved on day 1 of cycle 16, therapy was discontinued. If not, patients received acalabrutinib and venetoclax until cycle 24.
The median follow-up was 54.8 months, and the median number of cycles was 25. Approximately 42% of patients achieved the primary endpoint of bone marrow–undetectable MRD at day 1 of cycle 16, and the best overall response rate was 98.6%. Overall rates of best peripheral blood- and bone marrow–undetectable MRD were 94% and 85%, respectively. Of note, 79% of patients who achieved bone marrow–undetectable MRD chose to discontinue treatment after cycles 15 and 24, with a median time to treatment discontinuation of 27.5 months. Overall, the 4-year progression-free and overall survival rates were 89% and 99%, respectively. Neutropenia (73%) and thrombocytopenia (72%) were the most common hematologic toxicities, with headache (76%) and bruising (66%) being the most common nonhematologic toxicities.
Disclosure: For full disclosures of the study authors, visit ash.confex.com.
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