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Background: Combinatory strategies with carfilzomib (CFZ), a second-generation proteasome inhibitor, plus dexamethasone (DEX) with or without lenalidomide (LEN) have shown promising efficacy for patients with relapsed/refractory multiple myeloma (RRMM) in pivotal clinical trials. However, their effects on patients who were resistance to bortezomib (BTZ) and/or LEN have not been fully evaluated in a daily practice setting., Aims: To evaluate the real-world efficacy and safety of CFZ-based treatments; that is, CFZ with LEN plus DEX (KRD therapy) and CFZ with DEX (KD therapy), in Asian patients, we conducted a multicenter pilot prospective observational study in the Kyoto Clinical Hematology Study Group., Methods and Results: All 50 patients with RRMM enrolled in this study were treated with CFZ-based treatments between 2017 and 2019. KRD and KD were administered to 31 and 19 patients, respectively. The overall response rates (ORRs) were 80.6% with KRD and 73.7% with KD. Two-year progression-free survival (PFS) and overall survival (OS) were 58.5% and 79.7% with KRD, and 23.1% and 52.6% with KD. By multivariate analysis, refractoriness to BTZ and to LEN were identified as independent unfavorable factors for both PFS and OS. The common non-hematologic AEs included hypertension (42.0%), fever (24.0%), fatigue (24.0%), and infection (16.0%). No serious heart failure was observed. This study is registered as UMIN000025108., Conclusion: This study suggests the need of the development of novel CFZ-containing strategy which can overcome the refractoriness to BTZ and/or LEN, while both KRD and KD were shown to be mostly feasible in Asian patients in a daily practice setting., (© 2021 The Authors. Cancer Reports published by Wiley Periodicals LLC.)

A total of 129 symptomatic patients with multiple myeloma (MM) who underwent high-dose chemotherapy with autologous stem cell transplantation (HDT/ASCT) were analyzed. The 4-year overall survival (OS) of patients with maintenance ( n  = 82) was 80%, whereas that of patients without maintenance ( n  = 47) was 72% ( p  = 0.426). The 4-year progression-free survival (PFS) of patients with maintenance was 38%, whereas that of patients without maintenance was 27% ( p  = 0.088). Multivariate analysis revealed that an International Staging System score ≥2 was associated with worse PFS (hazard ratio 1.62, p  = 0.043). Among the 129 patients, two were excluded owing to early relapse, 50 patients achieved complete response (CR), and 77 patients failed to achieve CR. Patients who achieved CR showed better 4-year PFS than those who failed to achieve CR (41% vs. 30%, p  = 0.027); however, 4-year OS was not different (76% vs. 82%, p  = 0.971). In patients who achieved CR, 4-year OS with/without maintenance was 74%/81% ( p  = 0.357), 4-year PFS with/without maintenance was 42%/40% ( p  = 0.954). In patients who failed to achieve CR, the 4-year OS with/without maintenance was 97%/91% ( p  = 0.107), and 4-year PFS with/without maintenance was 36%/16% ( p  < 0.001). In patients who failed to achieve CR, maintenance significantly improved the PFS. Maintenance after HDT/ASCT can prolong PFS in patients who fail to achieve CR in real-world settings., Competing Interests: This work was supported by Bristol‐Myers Squibb/Celgene K.K.All authors received research funding from Ono Pharmaceutical Co., Ltd., Fujimoto Pharmaceutical Corporation. HT, HS, AT, IM, JKA, TI, KI, SK, and SY received honoraria from Novartis Pharma K.K. JKU, HT, JKA, AT, HS, IM, SF, TI, KI, MH, SK, and SY received honoraria from Bristol‐Myers Squibb/Celgene K.K. IM, HS, JKU, SF, MH, and SY received honoraria from Janssen Pharmaceutical K.K. SF, JKA, TI, HS, KI, MH, and SK received honoraria from Takeda Pharmaceutical Company, Limited. AT, HS, JKA, KI, MH, and SK received honoraria from Kyowa Kirin Co., Ltd. HS, JKA, KI, MH, and SK received honoraria from Chugai Pharmaceutical Co., Ltd. At, JKA, IM, KI, MH, and SK received honoraria from Astellas Pharma Inc. SF, HS, MH, and SY received honoraria from Sanofi K.K. SF, HS, MH, SK, and SY received honoraria from Ono Pharmaceutical Co., Ltd. JKA, IM, KI, and MH received honoraria from Otsuka Pharmaceutical Co., Ltd. JKA and IM received honoraria from Daiichi Sankyo Company, Limited. IM received honoraria from Pfizer Japan Inc. and Amgen inc. IM and TI received honoraria from AbbVie GK. AT, JKA, and MH received honoraria from MSD K.K. HS received honoraria from AstraZeneca K.K., Sanofi K.K. AT, KI, and MH received honoraria from Nippon Shinyaku Co., Ltd. JKA received honoraria from JCR Pharmaceuticals Co., Ltd. JKU and SK received honoraria from Fujimoto Pharmaceutical Corporation. KI and MH received honoraria from Dainippon Sumitomo Pharma Co., Ltd. MH received honoraria from Pfizer Japan Inc., Japan Blood Products Organization, Mochida Pharmaceutical CO., Ltd., and Mundipharma K.K. MH received honoraria from Eisai Co., Ltd. JKU, AT, HS, and TI received research funding from Bristol‐Myers Squibb. IM, TI, and HS received research funding from AbbVie GK. AT and HS received research funding from Ono Pharmaceutical Co., Ltd. IM, HS, and SY received research funding from Chugai Pharmaceutical Co., Ltd. IM and HS received research funding from Novartis Pharma K.K. IM received research funding from Takeda Pharmaceutical Company, Limited., Pfizer Japan Inc., Eisai Co., Ltd., and Alexion Pharmaceuticals, Inc. HS received research funding from Janssen Pharmaceutical K.K., Sanofi K.K., and AstraZeneca K.K. MH received research funding from Taiho Pharmaceutical Co., Ltd., Teijin Limited, Eisai Co., Ltd., Nihon Pharmaceutical Co., Ltd., and JCR Pharmaceuticals Co., Ltd. AT, IM received scholarship grant from Takeda Pharmaceutical Company, Limited., Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Nippon Shinyaku Co., Ltd., Astellas Pharma Inc., Otsuka Pharmaceutical Co., Ltd., Sanofi K.K., Shionogi & Co., Ltd., and AbbVie GK. AT, HT, and IM received scholarship grant from Kyowa Kirin Co., Ltd. AT received scholarship grant from Ohara Pharmaceutical Co., Ltd, and Kinshikouraininjin., the Japanese Society of Hematology. IM received scholarship grant from Ono Pharmaceutical Co., Ltd., Dainippon Sumitomo Pharma Co., Ltd., Asahi Kasei Pharma Corporation., Taiho Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Corporation., Novartis Pharma K.K., and MSD K.K. JKU received scholarship grant from Fujimoto Pharmaceutical Corporation., (© 2021 The Authors. eJHaem published by British Society for Haematology and John Wiley & Sons Ltd.)