In a side-by-side comparison study in patients with relapsed/refractory (R/R) chronic lymphocytic leukemia, the Bruton tyrosine kinase inhibitor acalabrutinib showed enhanced selectivity and tolerability compared to ibrutinib.

Acalabrutinib 100 mg twice daily was administered to 43 patients with marginal zone lymphoma (MZL) and at least one prior therapy in the R/R MZL cohort (phase 2) of a phase 1b/2 trial until disease progression or unacceptable toxicity [median age 69 years (range 42-84); median one (1-4) prior systemic regimens]. Around 13.3 months on average were followed up (range 0.5–45.5). The investigator-assessed overall response rate was 53% [95% CI 36%-69%] among the 40 patients who could be evaluated for response, with 5 (13%) full responses.

Of the 40 treated individuals, 40 (93%) experienced tumor shrinkage. The median response time was 2.9 months (median duration of response not estimable). The estimated 12-month PFS rate was 67%, with a median progression-free survival (PFS) of 27.4 months. About 5 patients passed away (4 due to illness progression and 1 from septic shock). The most frequent adverse effects (AEs) in 17 patients (40%) were neutropenia (14%), anemia, dyspnea, tiredness, and thrombocytopenia (5% each). Atrial fibrillation/flutter and severe hemorrhage were not documented, while 5% of patients had hypertension. Three (7%) individuals’ medication was stopped because of AEs. In individuals with R/R MZL, acalabrutinib was active and well tolerated.