Safety and efficacy of daratumumab in Japanese patients with relapsed or refractory multiple myeloma: a multicenter, phase 1, dose-escalation study
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Safety, efficacy, and pharmacokinetics (PK) of daratumumab as a monotherapy were investigated in Japanese patients with relapsed/refractory multiple myeloma (MM). This multicenter, dose-escalation study included patients (age ≥20 years) with ≥2 prior therapies. Daratumumab was administered intravenously: 8 mg/kg (n = 4) and 16 mg/kg (n = 5). The primary endpoint was safety. Secondary endpoints included objective response, overall response rate (ORR), progression-free survival (PFS), PK, and immunogenicity. Daratumumab was well-tolerated. Eight patients experienced Grade ≥3 adverse event (AE). Four serious AEs were observed in three patients; no AEs leading to death. Infusion-related reactions occurred in four (44%) patients and were Grade 1 or 2. Mean (SD) cumulative dose of daratumumab was 132.3 (108.5) mg/kg. Median duration of follow-up was 10.5 months (range 2.3, 16.4) for 8 mg/kg cohort and 9.9 months (range 1.7, 13.2) for 16 mg/kg cohort. The ORR (44%) comprised 1 and 3 partial responses in 8 and 16 mg/kg cohorts, respectively. The median PFS was 6 months for 8 mg/kg cohort, 9.5 months for 16 mg/kg cohort. Daratumumab serum exposure was increased with increasing dose. Antibodies against daratumumab were not observed. Daratumumab was safe and well-tolerated in Japanese patients with relapsed /refractory MM.
KeywordsDaratumumab Efficacy Multiple myeloma Safety
Compliance with ethical standards
Conflict of interest
M.A. and M.I. are employees of Janssen Pharmaceutical. K.S. received honoraria from Celgene and Janssen; S.I. from Celgene, Janssen, Ono Pharmaceutical, Takeda Pharmaceutical and Bristol-Myers; S.I., S.K., and M.R. received research funding from Ono Pharmaceutical, Lilly, Celgene, Janssen, Kyowa Hakko Kirin, Sanofi, Takeda Pharmaceutical, Novartis; S.I., S.K., and M.R. received subsidies or donations from Chugai Pharmaceutical, Kyowa Hakko Kirin, Teijin Pharma, Astellas, Toyama Chemical. The study was funded by Janssen Pharmaceutical. All authors had full access to all the data in the study and had final responsibility for the decision to submit for publication. All authors met the International Council of Medical Journal Editors’ criteria for authorship, and anyone who met those criteria is listed as an author. All authors have read and approved the final manuscript for submission.
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