A phase 1/2 study of carfilzomib in Japanese patients with relapsed and/or refractory multiple myeloma |
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| Authors: | Takashi Watanabe Kensei Tobinai Morio Matsumoto Kenshi Suzuki Kazutaka Sunami Tadao Ishida Kiyoshi Ando Takaaki Chou Shuji Ozaki Masafumi Taniwaki Naokuni Uike Hirohiko Shibayama Kiyohiko Hatake Koji Izutsu Takayuki Ishikawa Yoshihisa Shumiya Tomohisa Kashihara Shinsuke Iida |
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| Affiliation: | 1. Department of Haematology, National Cancer Centre Hospital, Tokyo, Japan;2. Department of Haematology, Komaki City Hospital, Komaki, Japan;3. Department of Haematology, National Hospital Organization Nishigunma National Hospital, Shibukawa, Japan;4. Department of Haematology, Japanese Red Cross Medical Centre, Tokyo, Japan;5. Department of Haematology, National Hospital Organization Okayama Medical Centre, Okayama, Japan;6. Department of Gastroenterology, Rheumatology and Clinical Immunology, Sapporo Medical University School of Medicine, Sapporo, Japan;7. Department of Haematology and Oncology, Tokai University School of Medicine, Isehara, Japan;8. Department of Internal Medicine, Niigata Cancer Centre Hospital, Niigata, Japan;9. Department of Haematology, Tokushima Prefectural Central Hospital, Tokushima, Japan;10. Division of Haematology and Oncology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan;11. Department of Haematology, National Hospital Organization Kyushu Cancer Centre, Fukuoka, Japan;12. Department of Haematology and Oncology, Osaka University Graduate School of Medicine, Suita, Japan;13. Department of Haematology and Oncology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan;14. Department of Haematology, Toranomon Hospital, Tokyo, Japan;15. Department of Haematology, Kobe City Medical Centre General Hospital, Kobe, Japan;16. Department of Oncology Clinical Development Planning, Ono Pharmaceutical Co., Ltd., Osaka, Japan;17. Department of Haematology and Oncology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan |
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| Abstract: | We conducted a phase 1/2 study of single‐agent carfilzomib in Japanese patients with relapsed/refractory multiple myeloma. Safety, pharmacokinetics and pharmacodynamics of carfilzomib were examined in phase 1. The primary endpoint in phase 2 was the overall response rate (ORR). Carfilzomib was administered in a twice‐weekly, consecutive‐day dosing schedule. In Phase 1, doses of 15 or 20 mg/m2 were administered on this schedule or 20 mg/m2 on Days 1 and 2 of Cycle 1 and then 27 mg/m2 in the 20/27 mg/m2 cohort. Patients had a median of five prior therapies, including bortezomib and an immunomodulatory agent. The dose level did not reach the maximum tolerated dose. The most common adverse events were haematological. Notably, carfilzomib either induced new hypertension (n = 4) or aggravated previously existing hypertension (n = 6) in 10 of 50 patients. Four of the eight patients who previously experienced peripheral neuropathy (PN) experienced a recurrence with carfilzomib use, but no new cases of PN occurred. The ORR of the 20/27 mg/m2 40 patient cohort was similar to that in the pivotal US study. The dose was efficacious and tolerable in heavily pre‐treated Japanese patients; however, meticulous control of hypertension may be necessary for further carfilzomib use. |
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| Keywords: | multiple myeloma carfilzomib hypertension peripheral neuropathy cardiovascular AEs |
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