Carfilzomib monotherapy in Japanese patients with relapsed or refractory multiple myeloma: A phase 1/2 study

• Published in: Cancer science 2019-09, Vol.110 (9), p.2924-2932
• Main Authors: Iida, Shinsuke, Watanabe, Takashi, Matsumoto, Morio, Suzuki, Kenshi, Sunami, Kazutaka, Ishida, Tadao, Ando, Kiyoshi, Chou, Takaaki, Ozaki, Shuji, Taniwaki, Masafumi, Uike, Naokuni, Shibayama, Hirohiko, Hatake, Kiyohiko, Izutsu, Koji, Ishikawa, Takayuki, Shumiya, Yoshihisa, Tobinai, Kensei
• Format: Article
• Language: English
• Subjects: Aged; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - adverse effects; carfilzomib; Chemotherapy; clinical trial; Dosage; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug dosages; Drug Resistance, Neoplasm; FDA approval; Female; Follow-Up Studies; Hematology; hematopoiesis; Humans; Japan - epidemiology; Japanese; Leukopenia; Leukopenia - chemically induced; Leukopenia - epidemiology; Lymphopenia; Male; Maximum Tolerated Dose; Middle Aged; Multiple myeloma; Multiple Myeloma - drug therapy; Multiple Myeloma - mortality; Multiple Myeloma - pathology; Neoplasm Recurrence, Local - drug therapy; Neoplasm Recurrence, Local - mortality; Neoplasm Recurrence, Local - pathology; Neutropenia; Neutropenia - chemically induced; Neutropenia - epidemiology; Neutrophils; Oligopeptides - administration & dosage; Oligopeptides - adverse effects; Original; Pharmaceuticals; Progression-Free Survival; Studies; Survival; Survival Analysis; Technical communication
• ISSN: 1347-9032; 1349-7006
• DOI: 10.1111/cas.14139

This multicenter, open‐label phase 1/2 study evaluated single‐agent carfilzomib in 50 heavily pretreated Japanese patients with relapsed/refractory multiple myeloma (median of five prior treatments). In phase 1, patients were dosed at three levels: 15, 20, or 20/27 mg/m2. Maximum tolerated dosage was not reached at the tolerability evaluation. Patients in phase 2 were treated with 20/27 mg/m2 carfilzomib. Median duration of exposure to carfilzomib in the 20/27 mg/m2 group at this final analysis was 4.7 months (range: 0.3‐39.4). Overall response rate in the 20/27 mg/m2 group, primary endpoint of the study, was 22.5% (n = 9) (95% confidence interval, 12.3‐37.5) with 2.5% (n = 1) stringent complete response. Median progression‐free survival and overall survival in the 20/27 mg/m2 group were 5.1 months (95% CI, 2.8‐13.6) and 22.9 months (95% CI, 14.1‐not estimable), respectively. Frequently occurring grade ≥3 adverse events in the 20/27 mg/m2 group included lymphopenia (72.5%), neutropenia (40.0%), and leukopenia (32.5%). Giving long‐term carfilzomib monotherapy led to long‐term overall survival for heavily pretreated multiple myeloma patients with a favorable safety profile. Carfilzomib monotherapy can be a good option for heavily pretreated multiple myeloma patients. This multicenter, open‐label phase 1/2 study evaluated single‐agent carfilzomib in 50 heavily pretreated Japanese patients with relapsed/refractory multiple myeloma (in phase 1, patients were dosed at three levels: 15, 20, or 20/27 mg/m2; in phase 2, patients were treated with 20/27 mg/m2 carfilzomib). Median duration of exposure to carfilzomib in the 20/27 mg/m2 group at this final analysis was 4.7 months (range: 0.3‐39.4) and the overall response rate in the 20/27 mg/m2 group, the primary endpoint of the study, was 22.5% (n = 9) (95% confidence interval, 12.3‐37.5) with 2.5% (n = 1) stringent complete response. Giving long‐term carfilzomib monotherapy led to long‐term overall survival for heavily pretreated multiple myeloma patients with a favorable safety profile.