Safety and antitumor activity of acalabrutinib for relapsed/refractory B‐cell malignancies: A Japanese phase I study. Issue 6 (7th May 2021)

• Record Type: Journal Article
• Authors: Izutsu, Koji; Ando, Kiyoshi; Ennishi, Daisuke; Shibayama, Hirohiko; Suzumiya, Junji; Yamamoto, Kazuhito; Ichikawa, Satoshi; Kato, Koji; Kumagai, Kyoya; Patel, Priti; Iizumi, Sakura; Hayashi, Nobuya; Kawasumi, Hisashi; Murayama, Kosho; Nagai, Hirokazu
• Is Part Of: Cancer science. Volume 112:Issue 6(2021)
• Page Start: 2405
• Page End: 2415
• Publication Date: 2021-05-07
• Subjects: Bruton's tyrosine kinase -- chronic lymphocytic leukemia -- mantle cell lymphoma -- pharmacokinetics -- small lymphocytic lymphoma; Cancer -- Periodicals; Neoplasms -- Periodicals; Research -- Periodicals; Electronic journals; 616.994005
• DOI: 10.1111/cas.14886
• Languages: English
• ISSNs: 1347-9032

Abstract

Abstract : This multicenter, open‐label, phase I study assessed the safety and antitumor activity of acalabrutinib in Japanese patients with relapsed/refractory (r/r) B‐cell malignancies. Parts 1 (dose confirmation) and 2 (dose expansion) of this three‐part study are reported. Treatment was a single dose of 100 mg acalabrutinib (day 1), followed by a washout period and then twice daily 100 mg acalabrutinib in part 1, or twice daily 100 mg acalabrutinib in part 2. Patients from parts 1 and 2 with r/r chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), and r/r mantle cell lymphoma (MCL) were assessed as r/r CLL/SLL and r/r MCL cohorts, respectively. Twenty‐five patients received treatment (part 1, n = 6). Median age was 71.0 years. Nine (one patient from part 1) and 13 (two patients from part 1) patients were included in the r/r CLL/SLL and r/r MCL cohorts, respectively. Treatment‐related adverse events (AEs) occurred in 88% of patients (grade ≥3, 36%); the most common were headache (28%) and purpura (24%), both grade 1/2. No AEs resulted in treatment discontinuation or death. Median duration of treatment was 31, 20, and 7 months for part 1, r/r CLL/SLL cohort, and r/r MCL cohort, respectively. Overall response rate (ORR) was 89% and 62% for the r/r CLL/SLL and r/r MCL cohorts, respectively. The median progression‐free survival (PFS) was not reached for the r/r CLL/SLL cohort and was 7 months for the r/r MCL cohort. Acalabrutinib (100 mg twice daily) was generally safe and well‐tolerated in adult Japanese patients with B‐cell malignancies. Abstract : This phase I study assessed the safety and antitumor activity of acalabrutinib in Japanese patients with relapsed/refractory B‐cell malignancies. Twenty‐five patients received treatment, and adverse events occurred in 88% of patients; however, most were grade 1 or 2, and no adverse event resulted in treatment discontinuation. Acalabrutinib was generally safe and well‐tolerated in adult Japanese patients with B‐cell malignancies.