FDA

FDA greenlights oral combo for treatment-naive CLL/SLL

February 25, 2026

On February 19, 2026, FDA approved Calquence (acalabrutinib) tablets and capsules in combination with Venclexta (venetoclax) for adults with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

Efficacy

Efficacy was evaluated in AMPLIFY (NCT03836261), a randomized, multicenter trial in adult patients previously untreated for CLL without del(17p) or TP53 mutation. Patients were randomized to receive acalabrutinib and venetoclax (AV) or investigator’s choice of chemotherapy (fludarabine plus cyclophosphamide plus rituximab [FCR] or bendamustine plus rituximab [BR]).

The major efficacy outcome measure was progression-free survival (PFS) as assessed by independent review committee for the AV arm vs. the investigator’s choice arm (FCR/BR). Median duration of PFS follow-up was 42.6 months. Median PFS was not estimable (NE) (95% confidence interval, 51.1, NE) in the AV arm and 47.6 months (95% CI, 43.3, NE) in the FCR/BR arm (hazard ratio, 0.65; 95% CI, 0.49, 0.87; p-value 0.0038). With a median follow-up of 41.0 months, there were 18 (6%) deaths in the AV arm and 42 (14%) in the FCR/BR arm.

Safety

The acalabrutinib prescribing information includes warnings and precautions for serious and opportunistic infections, hemorrhage, cytopenias, second primary malignancies, cardiac arrythmias, and hepatotoxicity. The venetoclax prescribing information includes warnings and precautions for tumor lysis syndrome, neutropenia, infections, and embryo-fetal toxicity. In AMPLIFY, serious adverse reactions occurred in 25% of patients receiving AV, and serious or grade 3 or higher infections in 14%.

Recommended dosing

The recommended regimen for acalabrutinib in combination with venetoclax consists of up to 14 cycles of acalabrutinib and 12 cycles of venetoclax starting at cycle 3. Each cycle is 28 days. The recommended acalabrutinib dose is 100 mg taken orally approximately every 12 hours until disease progression, unacceptable toxicity, or completion of 14 cycles of treatment. Start venetoclax at 20 mg according to the 5-week ramp-up dosing schedule in the prescribing information. Following the ramp-up, the recommended venetoclax dose is 400 mg orally once daily until disease progression, unacceptable toxicity, or until the last day of cycle 14.

Sources:

FDA approves acalabrutinib with venetoclax for chronic lymphocytic leukemia or small lymphocytic lymphoma. [News release]. 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-acalabrutinib-venetoclax-chronic-lymphocytic-leukemia-or-small-lymphocytic-lymphoma

Calquence® plus venetoclax approved in the US as first all-oral, fixed-duration combination for patients with chronic lymphocytic leukemia in the 1st-line setting. [News release]. 2026. https://www.astrazeneca.com/media-centre/press-releases/2026/fixed-duration-calquence-combo-approved-in-us.html

US Food and Drug Administration (FDA) approves combination treatment of Venclexta® (venetoclax) and acalabrutinib for previously untreated patients with chronic lymphocytic leukemia (CLL). [News release]. 2026. https://www.astrazeneca.com/media-centre/press-releases/2026/fixed-duration-calquence-combo-approved-in-us.html

Calquence (acalabrutinib) [package insert]. AstraZeneca. https://drd9vrdh9yh09.cloudfront.net/50fd68b9-106b-4550-b5d0-12b045f8b184/e2a005a7-65a0-4388-a671-dc887815a938/e2a005a7-65a0-4388-a671-dc887815a938_viewable_rendition__v.pdf Revised February 2026. Accessed February 23, 2026.

Venclexta (venetoclax) [package insert]. Abbvie. https://www.rxabbvie.com/pdf/venclexta.pdf Revised February 2026. Accessed February 23, 2026.