Study Findings Support Long-Term Efficacy and Safety of Acalabrutinib in R/R CLL

Long-term follow-up of a phase 1/2 study demonstrated durable efficacy and safety of acalabrutinib monotherapy in patients with relapsed/refractory chronic lymphocytic leukemia/small lymphocytic leukemia (CLL/SLL), according to results published in Blood.1

Acalabrutinib, an oral selective Bruton tyrosine kinase (BTK) inhibitor, was approved in November 2019 by the US Food and Drug Administration (FDA) at a dose of 100 mg twice daily for the treatment of adult patients with CLL/SLL.2

This analysis included updated results from the initial phase 1/2 study of acalabrutinib in an expanded cohort of 134 adult patients with relapsed/refractory CLL/SLL with a median age of 66 years ( Identifier: NCT02029443) followed for a median of 41 months. While patients initially received acalabrutinib at a dose of either 200 mg once daily or 100 mg twice daily, only the latter dose of acalabrutinib was administered following a study amendment in May 2015 based on results of pharmacodynamics studies.

At data cutoff, more than half of study patients were still receiving acalabrutinib, with 21% of patients discontinuing acalabrutinib therapy due to progressive disease.

Overall response rate (ORR), including patients achieving a complete response, a partial response. or a partial response with lymphocytosis (PRL) was 94%, with PRL as best response in 6% of patients. Of note, ORR was 90% or higher in the subgroups of patients with disease characterized by del(17)(p13.1), 
del(11)(q22.3), unmutated immunoglobulin heavy variable (IGHV) genes, and complex karyotype characterized by 3 or more abnormalities. In addition, median duration of response (DOR) was not reached, with 45-month DOR estimated at 63% for those with PRL or better.

Median progression-free survival (PFS) for the overall study population was not reached at the time of the analysis, with 45-month PFS estimated at 62%. In the subgroups of patients with disease characterized by del(17)(p13.1), unmutated/mutated IGHV, complex karyotype, and del(11)(q22.3), median PFS was 36 months, not reached, 33 months, and not reached, respectively.

Regarding safety, grade 3 or higher adverse events occurred in 66% of patients, including neutropenia, pneumonia, hypertension, anemia, and diarrhea in 14%, 11%, 7%, 7%, and 5% of patients, respectively.

Eleven percent of patients discontinued acalabrutinib as a result of one or more adverse events. Adverse event-related death was reported in 7.5% of patients, with half of these attributed to pneumonia.

Atrial fibrillation of any grade occurred in 7% patients, with approximately 3% experiencing atrial fibrillation of at least grade 3. Major bleeding classified as grade 3 or higher, serious, or involving the CNS, was reported in 5% percent of patients.

“Notably, acalabrutinib with follow-up beyond 4 years has shown a decreased frequency of [adverse events] over time and no long-term safety issues to date,” the study authors noted.

In their concluding remarks, they further commented that “this updated and expanded study confirms the efficacy, durability of response, and long-term safety of acalabrutinib, justifying its further investigation in previously untreated and treated patients with CLL/SLL.”


  1. Byrd JC, Wierda WG, Schuh A, et al. Acalabrutinib monotherapy in patients with relapsed/refractory chronic lymphocytic leukemia: updated phase 2 resultsBlood. 2020;135:1204-1213.
  2. Acalabrutinib (Calquence®) [package insert]. 2019. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2019.

Originally published on Cancer Therapy Advisor