ASH 2024: Interim Results from the AMPLIFY Study Show Durable Responses with Acalabrutinib Plus Venetoclax in Treatment-Naïve CLL

Use of fixed-duration Bruton tyrosine kinase inhibitor (BTKi) therapy in treatment-naïve chronic lymphocytic leukemia (CLL) is complicated by the limited efficacy and safety concerns observed with first-generation BTKis. The safety and efficacy of second-generation BTKis in this setting has yet to be established, though; thus the phase III AMPLIFY study aimed to assess the use of fixed-duration acalabrutinib plus venetoclax (with or without obinutuzimab) vs chemoimmunotherapy in adults with treatment-naïve CLL. Interim results from this study were presented Foundation SAB member Jennifer R. Brown, MD, PhD of Dana-Farber Cancer Institute.

The study included 867 patients (median age, 61 years) who were randomized to receive either acalabrutinib plus venetoclax (AV), acalabrutinib/venetoclax plus obinutuzumab (AVO), or investigator’s choice of chemoimmunotherapy.

The overall response rate with AV and AVO was 92.8% and 92.7%, respectively, compared with 75.2% with chemoimmunotherapy. At a median 41 months of followup, progression-free survival with chemoimmunotherapy was 35% than with AV and 58% than with AVO. Overall survival benefits were also observed with AV vs chemoimmunotherapy. Serious adverse events occurred in 24.7% of participants in the AV group, 38.4% in the AVO group, and 27.4% in the chemoimmunotherapy group.

The investigators concluded that the second-generation BTKi fixed-dose AV and AVO combination regimens provided deep and durable responses with a manageable safety profile in first-line treatment of CLL. Final results from the study are pending.