Trends and Outcomes of Hematopoietic Stem Cell Transplantation for Malignant Lymphoma in Japan between 2006 and 2021

Introduction: Autologous hematopoietic stem cell transplantation (auto-HSCT) and allogeneic HSCT (allo-HSCT) are one of the therapeutic options for patients with malignant lymphoma (ML). Over the years, the role of HSCT for ML has been changing with the advent of new treatment strategies, such as chimeric antigen receptor T-cell (CAR-T), bispecific antibody, and molecular targeted agents. In this study, we investigated the changes in the HSCT landscape for ML in Japan over 16 years.

Methods: We conducted a registry-based analysis of auto- and allo-HSCT activities using data from the Japanese Transplant Registry Unified Management Program between 2006 and 2021. Patients aged over 16 years, diagnosed with mature B-, T- and NK-cell neoplasms, and undergoing their first auto-HSCT or first allo-HSCT were included.

Results: In total, 12,112 patients underwent their first auto-HSCT, and 4,773, including 1,399 after auto-HSCT, underwent their first allo-HSCT. The number of patients who received auto-HSCT increased from 5,538 in 2006-2013 (Period 1) to 6,574 in 2014-2021 (Period 2) (p < .001), while the number of patients who received allo-HSCT increased from 2,231 to 2,542 during the same periods (p < .001).

Regarding auto-HSCT, patients who received auto-HSCT included those with diffuse large B-cell lymphoma (DLBCL) (58%), T/NK-cell lymphoma (T/NK) (14%), follicular lymphoma (FL) (9%), mantle cell lymphoma (MCL) (7%), Hodgkin lymphoma (HL) (9%) and others (3%). The number of patients who received auto-HSCT increased in DLBCL [3,164 (Period 1) vs. 3,818 (Period 2), p < .001], MCL [324 (Period 1) vs. 512 (Period 2), p < .001], and HL [491 (Period 1) vs. 599 (Period 2), p < .001]. Significant changes were observed in the median age at the time of auto-HSCT [56 (Period 1) vs. 59 (Period 2), p < .001] and in performance status (PS) at the time of auto-HSCT [ECOG PS 2-4; 7.7% (Period 1) vs. 6.2% (Period 2), p < .001]. The frequency of patients in first complete remission (CR) or partial remission (PR) , that is upfront auto-SCT setting, decreased from 51.0% (Period 1) to 43.4% (Period 2) (p < .001). With a median follow-up time for survivors of 4.2 years (range 0-16.5) for patients who received auto-HSCT, 4-year overall survival (OS) tended to improve from 67.6% (Period 1) to 69.4% (Period 2) (p = .06).

As for allo-HSCT, patients who received allo-HSCT included those with DLBCL (29%), T/NK (38%), FL (16%), MCL (3%), HL (7%), and others (7%). The number of patients who received allo-HSCT increased in DLBCL [619 (Period 1) vs. 767 (Period 2), p < .001], T/NK [765 (Period 1) vs. 1,042 (Period 2), p < .001]; in contrast, the number of patients who received allo-HSCT decreased in FL [442 (Period 1) vs. 313 (Period 2), p < .001]. Significant changes included an increase in the median age at allo-HSCT [56 (Period 1) vs. 59 (Period 2), p < .001] and in PS at allo-HSCT [ECOG PS 2-4; 17.4% (Period 1) vs. 14.3% (Period 2), p = .006]. The number of patients who received allo-HSCT in first CR or PR increased from 17.1% (Period 1) to 21.2% (Period 2) (p < .001). Regarding donor/stem cell sources, bone marrow was most used until 2014, and cord blood in 2015. But, since 2016, the use of peripheral blood stem cell became the most common. The rate of patients used myeloablative conditioning protocols was not different between the 2 cohorts [35.5% (Period 1) vs. 35.4 (Period 2), p = .89]. With a median follow-up of 4.9 years (range 0-16.6), the 4-year OS of patients who received allo-HSCT in Period 2 was significantly improved compared to in Period 1 [41.8% (Period 1) vs. 44.6% (Period 2), p = .006]. The 4-year non-relapse mortality was not different between the 2 cohorts [30.4 % (Period 1) vs. 28.8 % (Period 2), p = .20].

There was no change in the number of patients with DLBCL who received auto-HSCT or allo-HSCT since the approval of CAR-T therapy for the treatment of relapsed/refractory DLBCL in Japan in 2019 (p = .13).

Conclusions: The number of HSCT is increasing in most of lymphoma type and its outcome is improving over time in Japan. One reason for this can be the development of supportive care enabled us to perform HSCT even in elderly patients. On the other hand, the number of HSCT for FL is decreasing due to the changes in the therapeutic strategy. Our results can serve as real-world benchmark data of transplant for ML in Japan, and provide valuable insights for future treatment in ML.

Muramatsu:Asahi Kasei Pharma Corporation: Honoraria. Fujimoto:Chugai: Honoraria; Meiji Seika: Honoraria; Nippon Kayaku: Honoraria; Sanofi: Honoraria. Izutsu:Ono Pharma, Symbio, Takeda: Consultancy, Honoraria; MSD, AstraZeneca, Genmab, Chugai, BMS, Kyowa Kirin, Novartis, AbbVie: Consultancy, Honoraria, Research Funding; Incyte, Bayer, O Oncology, Regeneron: Research Funding; Pfizer, Janssen, Gilead, Daiichi Sankyo: Honoraria, Research Funding; Beigene, Yakult, Otsuka: Consultancy, Research Funding; AstraZeneca, Eli Lily, Astellas, Ono Pharmaceuticals, Eisai, Chugai, Janssen, Symbio, Bristol Myers Squibb, Daiichi Sankyo, Otsuka, Abbvie, Takeda, Eli Lilly, Genmab, Kyowa Kirin, MSD, Astellas, Pfizer, MeijiSeika Pharma, Novartis, Nihon Kayaku, Gilead,: Honoraria; MSD, AstraZeneca, Abbvie, Incyte, Bristol Myers Squibb, Novartis, Bayer, Pfizer, Janssen, Yakult, Kyowa Kirin, Daiichi Sankyo, Chugai, Beigene, Genmab, LOXO Oncology, Otsuka, Regeneron, Gilead: Research Funding; AstraZeneca, Zenyaku, Ono Pharmaceuticals, Mitsubishi Tanabe Pharma, Eisai, Chugai, Bristol Myers Squibb, Takeda, Otsuka, Abbvie, Zenyaku, Kyowa Kirin, MSD, Carna Biosciences, Novartis, Yakult, Nihon Shinyaku, Abe Pharma, Eisai,Beigene: Consultancy. Kobayashi:SymBio: Honoraria; Pharmaceuticals: Honoraria; anssen Pharmaceutical: Honoraria; Sanofi: Honoraria; AstraZeneca: Honoraria; Abbvie: Honoraria; Bristol Myers Squibb: Honoraria; Chugai Pharmaceutical: Honoraria; Nippon Shinyaku: Honoraria. Yamamoto:Bristol Myers Squibb K.K.: Honoraria; AstraZeneca: Honoraria; Nihonkayaku Co.: Honoraria; Novartis Pharma Co.: Honoraria; Mundi Pharma Co.: Honoraria; Meiji Seika Pharma Co.: Honoraria; Daiichi Sankyo Co.: Honoraria; Chugai Pharmaceutical Co.: Honoraria; Eisai Co.: Honoraria; Genmab: Honoraria; Janssen Pharmaceutical KK.: Honoraria; Sanofi K.K.: Honoraria; Pfizer Japan Inc.: Honoraria; Ono Pharmaceutical Co.: Honoraria; Takeda Pharmaceutical Co.: Honoraria. Sawa:Kyowa Kirin Co., Ltd.: Honoraria. Kataoka:Asahi Genomics: Current equity holder in private company; Kyowa Kirin: Honoraria, Research Funding; Ono Pharmaceutical: Honoraria, Research Funding; Eisai: Honoraria, Research Funding; Teijin Pharma: Research Funding; Shionogi: Research Funding; Takeda Pharmaceutical: Honoraria, Research Funding; Mochida Pharmaceutical: Research Funding; Japan Blood Products Organization: Research Funding; Otsuka Pharmaceutical: Honoraria, Research Funding; Chugai Pharmaceutical: Honoraria, Research Funding; JCR Pharmaceuticals: Research Funding; Chordia Therapeutics: Research Funding; Asahi Kasei Pharma: Research Funding; Sumitomo Dainippon Pharma: Honoraria, Research Funding; SymBio Pharmaceuticals: Honoraria; AstraZeneca: Honoraria; Pfizer: Honoraria; Nippon Shinyaku: Honoraria; Daiichi Sankyo: Honoraria; AbbVie: Honoraria; Meiji Seika Pharma: Honoraria; Sanofi: Honoraria; Novartis: Honoraria; Celgene: Honoraria; Alexion Pharmaceuticals: Honoraria; Bristol-Myers Squibb: Honoraria; Janssen Pharmaceutical: Honoraria. Kanda:Asahi-kasei, MSD, Novartis, Pfizer, Sanofi, Chugai, Astellas, Kyowa-Kirin: Honoraria; Chugai, Kyowa-kirin, Asahi-kasei, Otsuka: Research Funding. Kanda:Eisai: Research Funding; AbbVie Inc.: Consultancy, Honoraria; Megakaryon Co: Consultancy; SymBio Pharmaceuticals, Ltd.: Consultancy; DAIICHI SANKYO Co., Ltd.: Consultancy, Honoraria; Novartis Pharma K.K.: Consultancy, Honoraria; Janssen Pharmaceutical K.K.: Consultancy, Honoraria; Astellas Pharma Inc.: Consultancy, Honoraria; CSL Behring K.K.: Honoraria; MSD K.K.: Honoraria; Sumitomo Dainippon Pharma Co., Ltd.: Honoraria; Takeda Pharmaceutical Company Limited: Honoraria; CHUGAI PHARMACEUTICAL Co., Ltd.: Honoraria; Amgen Pharma Inc.: Honoraria; Otsuka Pharmaceutical Co., Ltd.: Honoraria; Bristol-Myers Squibb Co: Honoraria; Ono Pharma Inc.: Honoraria; ASAHI KASEI PHARMA CORPORATION: Honoraria; Sanofi K.K.: Honoraria; asclepia: Honoraria; Kyowa Kirin Co., Ltd: Honoraria; Nippon Shinyaku Co., Ltd.: Honoraria; NIPPON KAYAKU CO．，LTD．: Honoraria. Kuroda:Janssen Pharmaceutical, AbbVie, Pfizer, BeiGene, Bristol Myers Squibb: Consultancy; Kyowa Kirin, Chugai Pharmaceutical, Japan Blood Product Organization, Sumitomo Pharmaceutical, Otsuka Pharmaceutical, Asahikasei, Taiho Pharmaceutical, Mochida Pharmaceutical: Research Funding; Bristol Myers Squibb, Pfizer, Janssen Pharmaceutical: Membership on an entity's Board of Directors or advisory committees; Janssen Pharmaceutical, Kyowa Kirin, Chugai Pharmaceutical, Ono Pharmaceutical, Sanofi, Bristol Myers Squibb, Novartis, AbbVie, Pfizer, Astellas Pharmaceutical, Nippon Shinyaku, Genmab, Pharma Essentia Japan: Honoraria. Suzuki:Chugai, Kyowa-Kirin, Shionogi, Taiho, Eisai, Ohtsuka: Research Funding; Chugai, Kyowa-Kirin, AbbVie, Bristol-Meyers Squibb, Eisai, Ohtsuka, MSD, Janssen, Takeda, Meiji-Seika, Novartis, AstraZeneca: Honoraria.