TY - JOUR
T1 - Randomised phase II study to optimise melphalan, prednisolone, and bortezomib in untreated multiple myeloma (JCOG1105)
AU - Maruyama, Dai
AU - Iida, Shinsuke
AU - Ogawa, Gakuto
AU - Fukuhara, Noriko
AU - Seo, Sachiko
AU - Miyazaki, Kana
AU - Yoshimitsu, Makoto
AU - Kuroda, Junya
AU - Tsukamoto, Norifumi
AU - Tsujimura, Hideki
AU - Hangaishi, Akira
AU - Yamauchi, Takahiro
AU - Utsumi, Takahiko
AU - Mizuno, Ishikazu
AU - Takamatsu, Yasushi
AU - Nagata, Yasuyuki
AU - Minauchi, Koichiro
AU - Ohtsuka, Eiichi
AU - Hanamura, Ichiro
AU - Yoshida, Shinichiro
AU - Yamasaki, Satoshi
AU - Suehiro, Youko
AU - Kamiyama, Yutaro
AU - Tsukasaki, Kunihiro
AU - Nagai, Hirokazu
N1 - Funding Information:
DM reports research funding from Janssen Pharmaceutical, Takeda Pharmaceutical, Eisai, Chugai Pharmaceutical, Ono Pharmaceutical, Celgene, MSD, Astellas Pharma, Amgen BioPharma, Otsuka Pharmaceutical, Novartis Pharma, Kyowa Kirin, Sanofi, Bristol‐Myers Squibb; honoraria from Janssen Pharmaceutical, Takeda Pharmaceutical, Eisai, Chugai Pharmaceutical, Ono Pharmaceutical, Celgene, Kyowa Kirin, MSD, Zenyaku Kogyo, Asahi Kasei Pharma, Bristol‐Myers Squibb, Daiichi Sankyo, AstraZeneca, Mundipharma, Nippon Shinyaku, Synmosa Biopharma Corporation. SI reports research funding from Chugai, Kyowa‐Hakko Kirin, Takeda, Ono, Janssen, Bristol‐Myers Squibb, MSD, Celgene, Daiichi Sankyo, Gilead, Abbvie, Sanofi; honoraria from Janssen, Celgene, Takeda, Daiichi Sankyo, Ono. Bristol‐Myers Squibb. GO has nothing to disclose. NF reports research funding from AbbVie, Bayer, Celgene, Eisai, Gilead, Solasia Pharma, Takeda; honoraria from Celgene, Chugai, Eisai, Janssen, Kyowa Hakko kirin, Mochida, Mundi, Nippon Shinyaku, Ono, Takeda, Zenyaku. SS reports consultancy in Janssen. MK reports research funding from Kyowa Hakko Kirin, Astellas Pharma, Ono Pharmaceutical; honoraria from Chugai Pharma, Kyowa Kirin, Eisai, SymBio Pharmaceuticals, Celgene, Takeda, Nippon Shinyaku, Janssen Pharmaceutical. MY reports membership on an entity's board of directors, speaker's bureau, or its advisory committees of Novartis, Bristol‐Myer‐Squibb, Shire, Takeda, Chugai, Sanofi. JK reports research funding from Kyowa Kirin, Chugai Pharmaceutical, Ono Pharmaceutical, Sanofi, Eisai, Bristol‐Myers Squibb, Sysmex, Celgene, Astellas Pharma, Pfizer, Sumitomo Dainippon Pharma, Fujimoto Pharmaceutica; membership on an entity's board of directors, speaker's bureau, or its advisory committees of Janssen Pharmaceutical K.K., Celgene, Bristol‐Myers Squibb, Ono Pharmaceutical, Takeda Pharmaceutical. NT reports research funding from Kyowa Kirin, Chugai Pharmaceutical, Astellas Pharma, Takeda Pharmaceutical, Eisai, Pfizer, MSD. HT reports honoraria from Chugai Pharmaceutical, Kyowa Kirin, Takeda Pharmaceutical. AH has nothing to disclose. TY reports consultancy in Abbvie, Pfizer, Astellas; research funding from Solasia; any other financial relationship with Takeda, Nihon‐ShinYaku, Otsuka, Sanofi, Taiho, MSD, Eisai, Kyowa Kirin, Ono Pharmaceutical, Sumitomo Dainippon Pharma, Teijin, Chugai, Fuji. TU and IM have nothing to disclose. YT reports research funding from Takeda Pharmaceutical, Chugai Pharmaceutical, Kyowa Hakko Kirin, Ono Pharmaceutical, Astellas Pharma, TAIHO Pharmaceutical, Bristol‐Myers Squibb, Pfizer, Taisho Toyama Pharmaceutical, Celgene; membership on an entity's board of directors, speaker's bureau, or its advisory committees of Takeda Pharmaceutical, Ono Pharmaceutical. YN reports honoraria from Janssen Pharmaceutical, Celgene, Bristol‐Myers Squibb, Takeda Pharmaceutical, Ono Pharmaceutical, Novartis Pharma; membership on an entity's board of directors, speaker's bureau, or its advisory committees of Takeda Pharmaceutical. KoM and EO have nothing to disclose. IH reports research funding from Bristol‐Myers Squibb (BMS), MSD, Astellas, Otsuka, Ono Pharmaceutical, Kyowa Kirin, Sanofi, Shionogi, Zenyaku, Daiichi Sankyo, Taiho, Takeda, Chugai, Eli Lilly, Nihon Shinyaku, Novartis, Pfizer, Celgene, Fujimoto; honoraria from Celgene, Janssen, Takeda, Ono Pharmaceutical, BMS, Novartis, Daiichi Sankyo, Kyowa Kirin, Eisai, Nihon‐shinyaku, Pfizer, AbbVie, Otsuka, Shionogi, Mundi Pharma; membership on an entity's board of directors, speaker's bureau, or its advisory committees of Celgene, Janssen, Takeda, Ono Pharmaceutical, BMS, Novartis, Daiichi Sankyo, Kyowa Kirin, Eisai, Nihon‐shinyaku, Pfizer, Shionogi, Mundi Pharma. ShY reports research funding from Takeda, Janssen; honoraria from Celgene, Takeda, Janssen, Ono. SaY has nothing to disclose. YS reports research funding from Chugai Pharma, Kyowa Hakko Kirin, Taiho Pharma, Teijin Pharma, Fuji Pharma. YK has nothing to disclose. KuT reports consultancy in Daiichi Sankyo, Ono Pharma, HUYA; research funding from HUYA, Chugai Pharma, Eisai, Bayer, Celgene; honoraria from Chugai Pharma, Celgene, Mundi Pharma, Kyowa Kirin. HN reports research funding from Janssen Pharmaceutical, Celgene, Mundi Pharma, Bayer Pharma, AbbVie, Takeda Pharmaceutical, Kyowa Kirin, Eisai, Bristol‐Myers Squibb, Ono Pharmaceutical, Zenyaku Kogyo, Solasia Pharma K.K., HUYA Bioscience International, AstraZeneca, SymBio Pharmaceuticals Limited, Otsuka Pharmaceutical, IQVIA, Chugai Pharmaceutical; honoraria from Janssen Pharmaceutical, Celgene, Mundi Pharma, Takeda Pharmaceutical, Kyowa Kirin, Eisai, Bristol‐Myers Squibb, Ono Pharmaceutical, Zenyaku Kogyo, AstraZeneca, Sanofi, Chugai Pharmaceutical, MSD, Novartis Pharma.
Funding Information:
We sincerely thank Shigeru Kusumoto, Suguru Fukuhara, Takashi Tokunaga for patient enrolment and their helpful comments on this study and the manuscript. We thank the JCOG Data Center/Operating Office (Kenichi Miyamoto and Yuko Watanabe) for their support in data management. We thank Kensei Tobinai for his great support and helpful comments on this study. We also thank the patients, physicians, nurses and staff members who participated in this multicentre trial for their excellent cooperation. The work was supported in part by National Cancer Center Research and Development Funds (26‐A‐4, 29‐A‐3), the Grant‐in‐Aid for Clinical Cancer Research (H26‐kakushin‐teki‐gan‐ippan‐074) from the Ministry of Health, Labour and Welfare of Japan, and by AMED under Grant Numbers JP16ck0106077 and JP19ck0106348 (D.M.).
Publisher Copyright:
© 2020 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd
PY - 2021/2
Y1 - 2021/2
N2 - We conducted a randomised phase II study to determine the optimal dose and schedule of melphalan, prednisone, and bortezomib (MPB) (jRCTs031180097). Transplant-ineligible untreated multiple myeloma patients were randomised to Arm A (twice weekly bortezomib in one six-week cycle followed by eight five-week cycles of four times once weekly bortezomib with melphalan and prednisolone on days 1–4) or Arm B (nine four-week cycles of three times once weekly bortezomib with melphalan and prednisolone on days 1–4). The primary end-point was complete response (CR) rate. Of 91 patients randomised to two arms, 88 were eligible. The median cumulative bortezomib doses were 45·8 and 35·1 mg/m2, CR rate was 18·6% [95% confidence interval (CI) 8·4–33·4] and 6·7% (95% CI 1·4–18·3), and the median progression-free survival (PFS) was 2·5 and 1·4 years in Arms A and B [hazard ratio (HR) 1·93 (95% CI 1·09–3·42)], respectively. Frequent grade ≥3 haematologic toxicities in Arms A and B were neutropenia (64·4% vs. 28·3%) and thrombocytopenia (35·6% vs. 10·9%). Grade 2/3 peripheral neuropathy was observed in 24·4/2·2% in Arm A and 8·7/0% in Arm B. In conclusion, Arm A was the more promising regimen, suggesting that the twice weekly schedule of bortezomib in the first cycle and higher cumulative dose of both bortezomib and melphalan influences the efficacy of modified MPB.
AB - We conducted a randomised phase II study to determine the optimal dose and schedule of melphalan, prednisone, and bortezomib (MPB) (jRCTs031180097). Transplant-ineligible untreated multiple myeloma patients were randomised to Arm A (twice weekly bortezomib in one six-week cycle followed by eight five-week cycles of four times once weekly bortezomib with melphalan and prednisolone on days 1–4) or Arm B (nine four-week cycles of three times once weekly bortezomib with melphalan and prednisolone on days 1–4). The primary end-point was complete response (CR) rate. Of 91 patients randomised to two arms, 88 were eligible. The median cumulative bortezomib doses were 45·8 and 35·1 mg/m2, CR rate was 18·6% [95% confidence interval (CI) 8·4–33·4] and 6·7% (95% CI 1·4–18·3), and the median progression-free survival (PFS) was 2·5 and 1·4 years in Arms A and B [hazard ratio (HR) 1·93 (95% CI 1·09–3·42)], respectively. Frequent grade ≥3 haematologic toxicities in Arms A and B were neutropenia (64·4% vs. 28·3%) and thrombocytopenia (35·6% vs. 10·9%). Grade 2/3 peripheral neuropathy was observed in 24·4/2·2% in Arm A and 8·7/0% in Arm B. In conclusion, Arm A was the more promising regimen, suggesting that the twice weekly schedule of bortezomib in the first cycle and higher cumulative dose of both bortezomib and melphalan influences the efficacy of modified MPB.
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U2 - 10.1111/bjh.16878
DO - 10.1111/bjh.16878
M3 - Article
C2 - 32583431
AN - SCOPUS:85087167253
VL - 192
SP - 531
EP - 541
JO - British Journal of Haematology
JF - British Journal of Haematology
SN - 0007-1048
IS - 3
ER -