Pooled analysis of safety data from clinical trials evaluating acalabrutinib monotherapy in mature B-cell malignancies.
Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K
washington; seattle; swedish cancer
Bruton tyrosine kinase (BTK) inhibition is an effective therapy for many B-cell malignancies. Acalabrutinib is a next-generation, potent, highly selective, covalent BTK inhibitor. To characterize acalabrutinib tolerability, we pooled safety data from 1040 patients with mature B-cell malignancies treated with acalabrutinib monotherapy in nine clinical studies (treatment-naïve: n = 366 [35%], relapsed/refractory: n = 674 [65%]; median [range] age: 67 [32-90] years; median [range] prior treatments: 1 [0-13]; median [range] duration of exposure: 24.6 [0.0-58.5] months). The most common adverse events (AEs) were headache (38%), diarrhea (37%), upper respiratory tract infection (22%), contusion (22%), nausea (22%), fatigue (21%), and cough (21%). Serious AEs (SAEs) occurred in 39% of patients; pneumonia (6%) was the only SAE that occurred in ≥2%. Deaths due to AEs occurred in 52 patients (5%); pneumonia (n = 8) was the only fatal AE to occur in ≥3 patients. AEs led to treatment discontinuation in 9%. Rates for the AEs of interest (all grades) included infections (67%), hemorrhages (46%), neutropenia (16%), anemia (14%), second primary malignancies (12%), thrombocytopenia (9%), hypertension (8%), and atrial fibrillation (4%). This pooled analysis confirmed acalabrutinib's tolerability and identified no newly emerging late toxicities, supporting acalabrutinib as a long-term treatment for patients with mature B-cell malignancies.
Furman, Richard R; Byrd, John C; Owen, Roger G; O'Brien, Susan M; Brown, Jennifer R; Hillmen, Peter; Stephens, Deborah M; Chernyukhin, Nataliya; Lezhava, Tamara; Hamdy, Ahmed M; Izumi, Raquel; Patel, Priti; Baek, Marshall; Christian, Beth; Dyer, Martin J S; Streetly, Matthew J; Sun, Clare; Rule, Simon; Wang, Michael; Ghia, Paolo; Jurczak, Wojciech; Pagel, John M; and Sharman, Jeff P, "Pooled analysis of safety data from clinical trials evaluating acalabrutinib monotherapy in mature B-cell malignancies." (2021). Articles, Abstracts, and Reports. 4971.