Pooled analysis of safety data from clinical trials evaluating acalabrutinib monotherapy in mature B-cell malignancies.

Adult Aged Aged, 80 and over Antineoplastic Agents / adverse effects Benzamides / adverse effects Clinical Trials as Topic / statistics & numerical data Drug-Related Side Effects and Adverse Reactions / epidemiology Female Follow-Up Studies Humans Leukemia, Lymphocytic, Chronic, B-Cell / drug therapy Male Middle Aged Prognosis Pyrazines / adverse effects Retrospective Studies Survival Rate United States / epidemiology

Journal

Leukemia

ISSN: 1476-5551

Titre abrégé: Leukemia

Pays: England

ID NLM: 8704895

Informations de publication

Date de publication:
11 2021

Historique:

received: 25 09 2020

accepted: 06 04 2021

revised: 19 03 2021

pubmed: 29 4 2021

medline: 31 12 2021

entrez: 28 4 2021

Statut: ppublish

Résumé

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.

Identifiants

DOI: 10.1038/s41375-021-01252-y PMID: 33907299

pubmed: 33907299

doi: 10.1038/s41375-021-01252-y

pii: 10.1038/s41375-021-01252-y

doi:

Substances chimiques

Antineoplastic Agents 0

Benzamides 0

Pyrazines 0

acalabrutinib I42748ELQW

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

Pagination

3201-3211

Subventions

Organisme : NCI NIH HHS

ID : R35 CA198183

Pays : United States

Informations de copyright

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