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Observational Study
. 2024 Jun;119(6):707-721.
doi: 10.1007/s12185-024-03754-8. Epub 2024 Mar 29.

Primary analysis of a prospective cohort study of Japanese patients with plasma cell neoplasms in the novel drug era (2016-2021)

Hirohiko Shibayama  1   2 , Mitsuhiro Itagaki  3 , Hiroshi Handa  4 , Akihiro Yokoyama  5 , Akio Saito  6 , Satoru Kosugi  7 , Shuichi Ota  8 , Makoto Yoshimitsu  9 , Yasuhiro Tanaka  10 , Shingo Kurahashi  11 , Shin-Ichi Fuchida  12 , Masaki Iino  13 , Takayuki Shimizu  14 , Yukiyoshi Moriuchi  15 , Kohtaro Toyama  16 , Kinuko Mitani  17 , Yutaka Tsukune  18 , Akiko Kada  19 , Hideto Tamura  20 , Masahiro Abe  21 , Hiromi Iwasaki  22 , Junya Kuroda  23 , Hiroyuki Takamatsu  24 , Kazutaka Sunami  25 , Masahiro Kizaki  26 , Tadao Ishida  27 , Toshiki Saito  19 , Itaru Matsumura  28 , Koichi Akashi  29 , Shinsuke Iida  30
Affiliations
Observational Study

Primary analysis of a prospective cohort study of Japanese patients with plasma cell neoplasms in the novel drug era (2016-2021)

Hirohiko Shibayama et al. Int J Hematol. 2024 Jun.

Abstract

The emergence of novel drugs has significantly improved outcomes of patients with plasma cell neoplasms (PCN). The Japanese Society of Hematology conducted a prospective observational study in newly diagnosed PCN patients between 2016 and 2021. The analysis focused on 1385 patients diagnosed with symptomatic PCN between 2016 and 2018. The primary endpoint was the 3-year overall survival (OS) rate among patients requiring treatment (n = 1284), which was 70.0% (95%CI 67.4-72.6%). Approximately 94% of these patients received novel drugs as frontline therapy. The 3-year OS rate was 90.3% (95%CI 86.6-93.1%) in the 25% of patients who received upfront autologous stem cell transplantation (ASCT), versus just 61.4% (95%CI 58.0-64.6%) in those who did not receive upfront ASCT. The only unfavorable prognostic factor that affected OS in ASCT recipients was an age of 65 or higher. For patients who did not receive ASCT, independent unfavorable prognostic factors included frontline treatment with conventional chemotherapies, international staging system score of 2/3, extramedullary tumors, and Freiberg comorbidity index of 2/3. This study unequivocally demonstrates that use of novel drugs improved OS in Japanese myeloma patients, and underscores the continued importance of upfront ASCT as the standard of care in the era of novel drugs.

Keywords: Novel drug era; Plasma cell neoplasms (PCN); Prospective cohort study; Three-year overall survival rate.

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Conflict of interest statement

HS reports honoraria from Takeda, Ono, Fujimoto, Janssen, Chugai, Eisai, Sanofi, AstraZeneca, Meiji Seika Pharma, and AbbVie, research funding from Ono, Bristol Myers Squibb, and AbbVie. HH reports honoraria from Janssen, Bristol Myers Squibb, and Takeda, research funding from Bristol Myers Squibb and Takeda. AY reports honoraria from Kyowa Kirin, Chugai, Janssen, Sanofi, Bristol Myers Squibb, Eisai, Takeda, and Nippon-Shinyaku, research funding from Kyowa Kirin. SK reports honoraria from Eisai, Mundipharma, Chugai, Otsuka, Sanofi, Meiji Seika Pharma, AbbVie, Ono, Janssen, Takeda, Amgen, Novartis, and Nippon-Shinyaku. SO reports honoraria from Bristol Myers Squibb, Takeda, AstraZeneca, Janssen, and Sanofi. MY reports honoraria from Takeda, Sanofi, Novartis, Bristol Myers Squibb, Meiji Seika Pharma, and Daiichi Sankyo. SF reports honoraria from Takeda, Sanofi, Janssen, Ono, and Bristol Myers Squibb. TS reports honoraria from Ono, Otsuka, Eisai, SymBio, Takeda, Chugai, Sumitomo, Daiichi Sankyo, MSD, and PharmaEssentia. KM reports honoraria from Kyowa Kirin, Chugai, MSD, Teijin Pharma, Nippon-Shinyaku, Taiho, Takeda, Otsuka, Nippon Kayaku, Daiichi Sankyo, Sumitomo, Novartis, Pfizer, Celgene, Bristol Myers Squibb, Mochida, AbbVie, Alexion, Ono, Sanofi, Janssen, SymBio, AstraZeneca, CSL Bering, Amgen, Fujimoto, Eisai, Meiji Seika Pharma, Asahi Kasei, and Astellas, research funding from Kyowa Kirin, Chugai, MSD, Teijin Pharma, Nippon-Shinyaku, Taiho, Takeda, Otsuka, Nippon Kayaku, Daiichi Sankyo, and Sumitomo, advisory board fees from Bristol Myers Squibb, Novartis, and Otsuka, travel expense from Kyowa Kirin. HT reports honoraria from Sanofi, Ono, Janssen, Takeda, Bristol Myers Squibb, and Chugai, research funding from Asahi Kasei. MA reports honoraria from Takeda, Bristol Myers Squibb, Janssen, Sanofi, Ono, and Daiichi Sankyo. HI reports honoraria from Sanofi, SymBio, Janssen, Daiichi Sankyo, Chugai, Takeda, AstraZeneca, AbbVie, and Kyowa Kirin. JK reports honoraria from Janssen, Bristol Myers Squibb, Ono, Chugai, Takeda, Sanofi, and Kyowa Kirin, research funding from Kyowa Kirin, Mochida, Sanofi, Chugai, Bristol Myers Squibb, Takeda, and Ono, consulting fees from Janssen and Bristol Myers Squibb. HT reports honoraria from Janssen, Ono, Sanofi, and Bristol Myers Squibb, consulting fee from SRL, research funding from Bristol Myers Squibb. KS reports honoraria from Ono, Bristol Myers Squibb, Janssen, and Sanofi, research funding from Ono, Celgene, AbbVie, Takeda, Sanofi, Bristol Myers Squibb, GSK, Chugai, Otsuka, Janssen, MSD, Novartis, Pfizer, and Kyowa Kirin. MK reports honoraria from Bristol Myers Squibb, Novartis, Janssen, MSD, Nippon-Shinyaku, Ono, Takeda, and Sumitomo, research funding from Ono, Takeda, Kyowa Kirin, Chugai, and Daiichi Sankyo. TI reports honoraria from Takeda, Sanofi, Janssen, Bristol Myers Squibb, and Ono, research funding from Takeda, Pfizer, Sanofi, Janssen, and Bristol Myers Squibb. IM reports honoraria from Bristol Myers Squibb, Novartis, Otsuka, Pfizer, Janssen, Astellas, Takeda, Daiichi Sankyo, Ono, Chugai, AstraZeneca, SymBio, AbbVie, and Amgen, research funding from Ono, Janssen, Nippon-Shinyaku, Kyowa Kirin, Sumitomo, Shionogi, Teijin Pharma, Boehringer Ingelheim, Sanofi, Chugai, Eisai, MSD, Asahi Kasei, Astellas, Takeda, Nihon Pharma, Daiichi Sankyo, AbbVie, Taiho, Mitsubishi Tanabe, Nippon Kayaku, CSL Behring, Mundipharma, Ayumi Pharma, Eli Lilly Japan, Actelion Pharma, and Amgen, consulting fee from Otsuka. KA reports honoraria from AbbVie, Eisai, Ono, Kyowa Kirin, Chugai, Pfizer, Bristol Myers Squibb, and Janssen, research funding from Otsuka, Kyowa Kirin, Asahi Kasei, AbbVie, Chugai, and Takeda. SI reports honoraria from Janssen, Bristol Myers Squibb, Takeda, Sanofi, Ono, and Pfizer, research funding from Chugai, Janssen, Bristol Myers Squibb, Sanofi, Daiichi Sankyo, Pfizer, Celgene, Novartis, Ono, Takeda, Amgen, Shionogi, AbbVie, Otsuka, Kyowa Kirin, and GSK, advisory board fees from Janssen, Bristol Myers Squibb, Pfizer, Sanofi, AbbVie, Otsuka, Novartis, and Takeda. All the other authors have no conflicts of interest to disclose.

Figures

Fig. 1
Fig. 1
Registered patients were allocated as this branch shown here. A total of 1385 (1349 plus 36) symptomatic PCN patients were analyzed in this report
Fig. 2
Fig. 2
Survival curves of the symptomatic PCN patients who needed any kinds of treatments (n = 1284) are shown. a Three-year overall survival (OS) rate was 70.0% (95%CI 67.4–72.6%). The median OS period was 69.3 months (95%CI 67.1-NE). b Three-year OS rates of the patients who received upfront ASCT (n = 342, blue line) and who did not receive ASCT as initial therapies (n = 922, red line) were 90.3% (95%CI 86.6–93.1%) and 61.4% (95%CI 58.0–64.6%), respectively. The median OS periods of the former and the latter patient groups were NE and 55.1 months (95%CI 47.4–67.7), respectively
Fig. 3
Fig. 3
Best responses according to the first line therapies are shown. a All patients, b patients who received upfront ASCT (ASCT) and those who did not receive ASCT (non-ASCT)
Fig. 4
Fig. 4
Progression free survival (PFS) curves of the symptomatic PCN patients are shown. a Three-year PFS rate was 43.0% (95%CI 40.2–45.8%). The median PFS period was 27.8 months (95%CI 24.8–30.4). b Three-year PFS rates of ASCT patients (blue line) and non-ASCT patients (red line) were 64.3% (95%CI 58.8–69.2%) and 34.0% (95%CI 30.8–37.3%), respectively. The median PFS periods of the former and the latter patient groups were 53.4 months (95%CI 44.6–65.0) and 19.9 months (95%CI 17.7–22.3), respectively. Two patients receiving ASCT who showed PD before ASCT were excluded from this PFS analysis. c Three-year PFS rate of non-ASCT patients with ISS 3 (green line) was significantly worse than that with ISS 1 (blue line). d Three-year PFS rate of non-ASCT patients with extramedullary tumors (EMD) (red line) was significantly worse than that without extramedullary tumors (blue line)
Fig. 5
Fig. 5
Time to next treatment (TNT) curves of the symptomatic PCN patients are shown. The median TNT of ASCT (blue line) and non-ASCT (red line) were 62.5 months (95% CI 53.4–NA) and 22.8 months (95% CI 20.7–25.5), respectively
See this image and copyright information in PMC

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