FDA Approves Acalabrutinib Combo in Frontline CLL/SLL

The FDA has approved fixed-duration acalabrutinib (Calquence) plus venetoclax (Venclecxta) as a first-line treatment for adults with chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL), according to a press release from the developer, AstraZeneca.¹

Supporting data for the approval came from the phase 3 AMPLIFY trial (NCT03836261) evaluating the acalabrutinib combination vs standard-of-care chemotherapy.² Topline data revealed a progression-free survival (PFS) rate of 77% at 3 years among patients who received the acalabrutinib regimen vs 67% of those in the comparator arm. Additionally, the median PFS was not reached and 47.6 months in each respective arm (HR, 0.65; 95% CI, 0.49-0.87; P = .0038).

The safety profile of acalabrutinib in the AMPLIFY trial was comparable with prior reports of the agent; no new safety signals emerged.

“The continuous regimens frequently used to treat [CLL] often come with [adverse] effects that may become burdensome to patients over time,” principal trial investigator Jennifer Brown, MD, PhD, director of the CLL Center of the Division of Hematologic Malignancies at Dana-Farber Cancer Institute and the Worthington and Margaret Collette Professor of Medicine at Harvard Medical School, stated in the press release.¹ “The US approval of the [acalabrutinib] combination offers patients an all-oral, 14-month, fixed-duration treatment option that is highly effective and well-tolerated, and gives physicians greater flexibility to tailor treatment plans for individual patient needs and goals.”

References

1. 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. AstraZeneca. February 20, 2026. Accessed February 20, 2026. https://tinyurl.com/38zbx96s
2. Study of acalabrutinib (ACP-196) in combination with venetoclax (ABT-199), with and without obinutuzumab (GA101) versus chemoimmunotherapy for previously untreated CLL (AMPLIFY). ClinicalTrials.gov. Updated December 27, 2024. Accessed February 20, 2026. https://tinyurl.com/52pr6875