FDA approves acalabrutinib with venetoclax for chronic lymphocytic leukemia or small lymphocytic lymphoma

FDA approval (Feb 19, 2026)

The US FDA approved acalabrutinib (Calquence) tablets and capsules in combination with venetoclax (Venclexta) for adults with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

Key evidence

Efficacy and safety were evaluated in AMPLIFY (NCT03836261), a randomized, multicenter trial in previously untreated CLL patients without del(17p) or TP53 mutation, comparing acalabrutinib + venetoclax (AV) vs investigator’s choice chemotherapy (FCR or BR).

• Primary endpoint: PFS by independent review committee.
• Median PFS follow-up: 42.6 months.
• Median PFS: NE (95% CI 51.1, NE) with AV vs 47.6 months (95% CI 43.3, NE) with FCR/BR; HR 0.65 (95% CI 0.49–0.87); p=0.0038.
• With median follow-up 41.0 months: 18 (6%) deaths with AV vs 42 (14%) with FCR/BR.

Safety and labeling highlights

Acalabrutinib labeling includes warnings/precautions for serious/opportunistic infections, hemorrhage, cytopenias, second primary malignancies, cardiac arrhythmias, and hepatotoxicity. Venetoclax labeling includes tumor lysis syndrome, neutropenia, infections, and embryo-fetal toxicity. In AMPLIFY, serious adverse reactions occurred in 25%; serious or grade ≥3 infections in 14%.

Regimen (label)

Up to 14 cycles of acalabrutinib and 12 cycles of venetoclax starting cycle 3 (28-day cycles). Venetoclax starts at 20 mg with a 5-week ramp-up to 400 mg daily per prescribing information.

The applications were granted orphan drug designation; FDA review used an Assessment Aid submission.