The multicenter phase 3 study randomized patients with R/R CLL 1:1 to receive acalabrutinib 100 mg orally twice daily or investigator’s choice of idelalisib plus rituximab or bendamustine plus rituximab until disease progression or unacceptable toxicity.
The efficacy of acalabrutinib monotherapy was maintained and showed a significant progression-free survival (PFS) benefit over standard-of-care regimens in patients with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL) after 3 years of follow-up, according to a session presented at the American Society of Hematology Annual Meeting & Exposition 2021.1
Acalabrutinib is a Bruton tyrosine kinase inhibitor (BTKi) intended for the treatment of adult patients with mantle cell lymphoma who have received at least 1 prior therapy. It is also currently indicated for the treatment of adult patients with CLL or small lymphocytic lymphoma (SLL), according to an AstraZeneca press release.2
The multicenter phase 3 study randomized patients with R/R CLL 1:1 to receive acalabrutinib 100 mg orally twice daily or investigator’s choice of idelalisib plus rituximab or bendamustine plus rituximab until disease progression or unacceptable toxicity.1
Out of 310 enrolled patients, acalabrutinib significantly sustained the investigator-assessed PFS versus idelalisib/bendamustine plus rituximab combinations at a median follow-up of 36 months. Additionally, the PFS benefit was consistently shown in high-risk subgroups.1
Median overall survival (OS) was not reached, and the 36-month OS rate was 80% for acalabrutinib versus 73% for idelalisib/bendamustine plus rituximab. The overall response rate was 83% for acalabrutinib versus 85% for idelalisib/bendamustine plus rituximab.1
The most commonly reported adverse events were headache, neutropenia, diarrhea, and upper respiratory tract infection for acalabrutinib. Diarrhea and neutropenia were the most common for idelalisib plus rituximab, whereas neutropenia, fatigue, infusion-related reaction, and nausea were the most common for bendamustine plus rituximab.1
Drug discontinuation occurred in 21% of patients administered acalabrutinib, 65% in idelalisib plus rituximab, and 17% in bendamustine plus rituximab. All-grade atrial fibrillation, all-grade hypertension, all-grade major hemorrhage, and all-grade second primary malignancies, excluding non-melanoma skin cancer, were noted in all combinations.1