FDA Approves Calquence Plus Venclexta for CLL and SLL

The Food and Drug Administration (FDA) has approved Calquence (acalabrutinib) tablets and capsules in combination with Venclexta (venetoclax) for adults with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), offering a new first-line treatment option for patients with these blood cancers.

The approval is based on results from the AMPLIFY trial, which evaluated the combination in adult patients with CLL who had not received prior treatment and did not have del(17p) or TP53 mutation. The study compared Calquence plus Venclexta with standard chemotherapy options selected by investigators.

Full prescribing information for Calquence and Venclexta will be posted on Drugs@FDA.

Calquence plus Venclexta improved progression-free survival

Efficacy was evaluated in AMPLIFY (NCT03836261), a randomized, multicenter trial. Patients were assigned to receive Calquence and Venclexta or investigator’s choice of chemotherapy, either fludarabine plus cyclophosphamide plus rituximab or bendamustine plus rituximab.

The main measure of effectiveness was progression-free survival, meaning the length of time during and after treatment that a patient lives without their cancer growing or spreading.

At a median progression-free survival follow-up of 42.6 months, median progression-free survival was not estimable in the Calquence plus Venclexta arm and was 47.6 months in the chemotherapy arm. The hazard ratio was 0.65, indicating a lower risk of disease progression or death with the combination compared with chemotherapy.

With a median follow-up of 41 months, there were 18 deaths (6%) in the Calquence plus Venclexta arm and 42 deaths (14%) in the chemotherapy arm.

AMPLIFY trial design and dosing schedule

AMPLIFY enrolled adult patients with CLL who had not previously received treatment and did not have del(17p) or TP53 mutation. The trial was randomized and conducted at multiple centers.

Patients in the combination arm received up to 14 cycles of Calquence and 12 cycles of Venclexta beginning at cycle 3. Each cycle lasted 28 days.

The recommended dose of Calquence is 100 mg taken orally approximately every 12 hours until disease progression, unacceptable toxicity or completion of 14 cycles of treatment.

Venclexta is started at 20 mg using a 5-week ramp-up dosing schedule described in the prescribing information. After the ramp-up, the recommended Venclexta dose is 400 mg taken orally once daily until disease progression, unacceptable toxicity or the last day of cycle 14.

The review of this application used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s evaluation. The applications were granted orphan drug designation.

Side effects and safety considerations

The prescribing information for Calquence includes warnings and precautions for serious and opportunistic infections, hemorrhage, cytopenias, second primary malignancies, cardiac arrhythmias and hepatotoxicity.

The prescribing information for Venclexta includes warnings and precautions for tumor lysis syndrome, neutropenia, infections and embryo-fetal toxicity.

In the AMPLIFY trial, serious side effects occurred in 25% of patients receiving Calquence plus Venclexta. Serious or grade 3 (severe) or higher infections occurred in 14% of patients in the combination arm.

References

1. “FDA approves acalabrutinib with venetoclax for chronic lymphocytic leukemia or small lymphocytic lymphoma” FDA. Feb. 19, 2026.

Editor's note: This article is for informational purposes only and is not a substitute for professional medical advice, as your own experience will be unique. Use this article to guide discussions with your oncologist. Content was generated with AI and reviewed by a human editor.

For more news on cancer updates, research and education, don’t forget to subscribe to CURE®’s newsletters here.