TY - JOUR
T1 - Pooled analysis of safety data from clinical trials evaluating acalabrutinib monotherapy in mature B-cell malignancies
AU - Furman, Richard R.
AU - Byrd, John C.
AU - Owen, Roger G.
AU - O’Brien, Susan M.
AU - Brown, Jennifer R.
AU - Hillmen, Peter
AU - Stephens, Deborah M.
AU - Chernyukhin, Nataliya
AU - Lezhava, Tamara
AU - Hamdy, Ahmed M.
AU - Izumi, Raquel
AU - Patel, Priti
AU - Baek, Marshall
AU - Christian, Beth
AU - Dyer, Martin J.S.
AU - Streetly, Matthew J.
AU - Sun, Clare
AU - Rule, Simon
AU - Wang, Michael
AU - Ghia, Paolo
AU - Jurczak, Wojciech
AU - Pagel, John M.
AU - Sharman, Jeff P.
N1 - Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2021/11
Y1 - 2021/11
N2 - 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.
AB - 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.
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U2 - 10.1038/s41375-021-01252-y
DO - 10.1038/s41375-021-01252-y
M3 - Article
C2 - 33907299
AN - SCOPUS:85105233422
SN - 0887-6924
VL - 35
SP - 3201
EP - 3211
JO - Leukemia
JF - Leukemia
IS - 11
ER -