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Jeremy S. Abramson, MD, MMSc
Jeremy S. Abramson, MD, MMSc
Posted: Monday, February 3, 2025
Jennifer R. Brown, MD, PhD, of Dana-Farber Cancer Institute, Boston, and colleagues suggested there are efficacy and/or safety limitations to existing fixed-duration Bruton’s tyrosine kinase (BTK) inhibitor–based regimens for chronic lymphocytic leukemia (CLL). During the 2024 American Society of Hematology (ASH) Annual Meeting & Exposition (Abstract 1009), these investigators presented the interim results from the AMPLIFY trial, which evaluated fixed-duration venetoclax plus a second-generation BKT inhibitor vs chemoimmunotherapy in this patient population.
“The combinations of acalabrutinib/venetoclax and acalabrutinib/venetoclax/obinutuzumab provided deep and durable responses with manageable safety profiles, with acalabrutinib/venetoclax offering the first all-oral fixed-duration regimen that combines venetoclax with a second-generation BTK inhibitor in fit patients with treatment-naive CLL,” concluded the investigators.
This phase III, open-label, randomized trial enrolled 867 patients with treatment-naive CLL who had an Eastern Cooperative Oncology Group performance status of up to 2 and did not harbor a del(17p) or TP53 mutation. Participants were randomly assigned 1:1:1 to receive acalabrutinib plus venetoclax (n = 291); acalabrutinib, venetoclax, and obinutuzumab (n = 286); or investigator’s choice of chemoimmunotherapy (fludarabine/cyclophosphamide/rituximab plus bendamustine/rituximab; n = 290).
At the median follow-up of 41 months, progression-free survival appeared to be significantly improved with acalabrutinib plus venetoclax (P = .0038) and with acalabrutinib, venetoclax, and obinutuzumab (P < .0001) vs the chemoimmunotherapy cohort. The median progression-free survival was not reached in either experimental arm and was 47.6 months among patients given chemotherapy. In addition, objective response rates were significantly higher among patients who received venetoclax-based treatment vs chemotherapy (P < .0001), and overall survival favored acalabrutinib plus venetoclax (P < .0001).
The chemoimmunotherapy group had the highest number of deaths, followed by the triplet and doublet groups (n = 42 vs 37 vs 18). The most commonly reported grade 3 or higher adverse event was neutropenia, affecting 35.2%, 32.4%, and 26.8% of patients in the acalabrutinib/venetoclax/obinutuzumab, chemoimmunotherapy, and acalabrutinib/venetoclax arms, respectively; serious adverse events affected 38.4%, 27.4%, and 24.7% of patients.
Disclosure: For full disclosures of the study authors, visit ash.confex.com.
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