On February 19, 2026, the FDA approved the combination of acalabrutinib (Calquence) and venetoclax (Venclexta) for adult patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).
The approval was based on the AMPLIFY trial (NCT03836261), a randomized, multicenter study involving previously untreated adults with CLL without del(17p) or TP53 mutations. Patients received either the acalabrutinib-venetoclax (AV) combination or investigator’s choice of chemotherapy (fludarabine, cyclophosphamide, and either rituximab or bendamustine and rituximab).
Progression-free survival (PFS) was the primary end point. At a median follow-up of 42.6 months, the AV arm showed superior PFS compared with the chemotherapy arm. Median PFS was not estimable (NE) in the AV group (95% CI, 51.1-NE) versus 47.6 months (95% CI, 43.3-NE) in the chemotherapy group (hazard ratio, 0.65; P=.0038). Mortality was also lower in the AV group with 18 deaths (6%) compared with 42 deaths (14%) in the chemotherapy arm.
The AV combination’s safety profile includes warnings for serious infections, hemorrhage, cytopenias, and cardiac arrhythmias (acalabrutinib) and tumor lysis syndrome, neutropenia, and embryo-fetal toxicity (venetoclax). Serious adverse reactions occurred in 25% of AV-treated patients, with grade ≥3 infections in 14%.
The regimen includes up to 14 cycles of acalabrutinib (100 mg orally every 12 hours) and 12 cycles of venetoclax (20 mg ramping to 400 mg daily).
This approval offers another treatment option for patients with CLL or SLL.
Source
- FDA approves acalabrutinib with venetoclax for chronic lymphocytic leukemia or small lymphocytic lymphoma. www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-acalabrutinib-venetoclax-chronic-lymphocytic-leukemia-or-small-lymphocytic-lymphoma