Safety and antitumor activity of acalabrutinib for relapsed/refractory B‐cell malignancies: A Japanese phase I study

Autor: Koji Izutsu, Kazuhito Yamamoto, Priti Patel, Satoshi Ichikawa, Hisashi Kawasumi, Kiyoshi Ando, Sakura Iizumi, Koji Kato, Hirohiko Shibayama, Junji Suzumiya, Kosho Murayama, Kyoya Kumagai, Nobuya Hayashi, Hirokazu Nagai, Daisuke Ennishi
Rok vydání: 2021
Předmět:
Male
0301 basic medicine
Cancer Research
Chronic lymphocytic leukemia
small lymphocytic lymphoma
Lymphoma
Mantle-Cell
Gastroenterology
0302 clinical medicine
Japan
immune system diseases
hemic and lymphatic diseases
Aged
80 and over
Headache
General Medicine
Middle Aged
Bruton's tyrosine kinase
Treatment Outcome
medicine.anatomical_structure
Oncology
Pyrazines
030220 oncology & carcinogenesis
Benzamides
Cohort
Original Article
Female
pharmacokinetics
medicine.medical_specialty
mantle cell lymphoma
Antineoplastic Agents
Drug Administration Schedule
03 medical and health sciences
Refractory
Pharmacokinetics
Clinical Research
Internal medicine
medicine
Humans
Adverse effect
Purpura
B cell
Aged
business.industry
Original Articles
medicine.disease
Leukemia
Lymphocytic
Chronic
B-Cell
Survival Analysis
Discontinuation
030104 developmental biology
chronic lymphocytic leukemia
Mantle cell lymphoma
Neoplasm Recurrence
Local
business
Zdroj: Cancer Science
ISSN: 1349-7006
1347-9032
DOI: 10.1111/cas.14886
Popis: 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.
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.
Databáze: OpenAIRE
Externí odkaz: