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2166 Allogeneic Hematopoietic Cell Transplantation for Patients with Relapsed or Refractory Diffuse Large B Cell Lymphoma with Stable or Progressive Disease

Program: Oral and Poster Abstracts
Session: 723. Allogeneic Transplantation: Long-term Follow-up, Complications, and Disease Recurrence: Poster I
Hematology Disease Topics & Pathways:
Research, Clinical Research, Registries
Saturday, December 7, 2024, 5:30 PM-7:30 PM

Kimimori Kamijo1*, Yoshimitsu Shimomura, MD, PhD2,3*, Naoyuki Uchida4, Satoshi Yoshihara, MD, PhD5, Takahiro Fukuda6*, Yasufumi Uehara, MD, PhD7*, Yasuo Mori, M.D., Ph.D.8*, Tetsuya Eto9*, Hikaru Kobayashi10*, Kentaro Serizawa, MD11*, Tatsuo Ichinohe, MD, PhD12*, Makoto Yoshimitsu, MD, PhD13, Junya Kanda, MD, PhD14*, Yoshiko Atsuta, MD, PhD15* and Shinichi Kako, MD, PhD16

1Department of Hematology, Rinku General Medical Center, Izumisanoshi, HYO, Japan
2Department of Hematology, Kobe City Medical Center General Hospital, Kobe, Japan
3Department of Environmental Medicine and Population Science, Graduate School of Medicine, Osaka University, Suita, Japan
4Department of Hematology, Federation of National Public Service Personnel Mutual Aid Associations TORANOMON HOSPITAL, Tokyo, Japan
5Department of Hematology, Hyogo Medical University Hospital, Nishinomiya, Japan
6Department of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, Japan
7Department of Hematology, Kitakyushu City Hospital Organization, Kitakyushu Municipal Medical Center, Kitakyushu, Japan
8Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medicine, Fukuoka, Japan
9Department of Hematology, Hamanomachi Hospital, Fukuoka, Japan
10Department of Hematology, Nagano Red Cross Hospital, Nagano, Japan
11Division of Hematology and Rheumatology, Department of Internal Medicine, Kindai University Hospital, Osakasayama, JPN
12Department of Hematology and Oncology, Research Institute For Radiation Biology and Medicine, Hiroshima University, Hiroshima, JPN
13Department of Hematology and Rheumatology, Graduate School of Medical and Dental Sciences, Kagoshima University Hospital, Kagoshima, Japan
14Department of Hematology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
15Japanese Data Center for Hematopoietic Cell Transplantation, Nagakute, Japan
16Division of Hematology, Jichi Medical University Saitama Medical Center, Saitama, Japan

Background

Allogeneic hematopoietic cell transplantation (HCT) is a curative treatment option for relapsed/refractory diffuse large B-cell lymphoma (r/rDLBCL). Despite the advent of chimeric antigen receptor T-cell (CAR-T) therapy, several barriers to it exist and prevent its widespread use, ruling out CAR-T therapy as an option for every patient with r/rDLBCL. In addition, up to approximately 60% of patients experience relapse after CAR-T cell therapy, and several studies have demonstrated the efficacy of allogeneic HCT in these patients. Therefore, allogeneic HCT still plays an important role even in the CAR-T era. However, limited data are available on allogeneic HCT in patients with r/rDLBCL who have stable disease (SD) or progressive disease (PD) at transplant. Therefore, this study investigated the outcomes and prognostic factors in patients with r/rDLBCL with SD or PD who underwent allogeneic HCT.

Methods

This study included 662 adult patients with r/rDLBCL who underwent their first allogeneic HCT with SD or PD between January 2001 and December 2018. Missing data were imputed considering the missing at random assumption. The primary endpoint was 5-year progression-free survival (PFS), and secondary endpoints were 5-year overall survival (OS), 5-year cumulative incidence of relapse/progression, and 5-year cumulative incidence of non-relapse mortality. The OS and PFS were evaluated using the log-rank test. The other endpoints were evaluated using Gray’s method. Prognostic factors for the primary endpoint were evaluated using the multivariable Cox proportional hazards model, considering age, sex, performance status (PS), HCT-specific comorbidity index, disease status (primary induction failure, early relapse, and late relapse), conditioning regimen, donor type (related vs. unrelated donor), donor source (bone marrow [BM], peripheral blood [PB], and cord blood), the recipient and donor sex (male recipient with female donor vs. others), graft-versus-host disease prophylaxis, previous history of autologous HCT and the interval between autologous and allogeneic HCT (no previous autologous HCT, relapse over 12 months after autologous HCT, and relapse within 12 months after autologous HCT), allogeneic HCT performed within 24 months after diagnosis, four or more lines of chemotherapy before allogeneic HCT, and years of allogeneic HCT. The impacts of the candidate factors are shown as hazard ratios (HRs) with 95% confidence intervals (CIs).

Results

The median age was 53 years (interquartile range, 45–59 years), and 369 (56%) patients were male. A total of 201 (31%) patients had PS of 2 or higher and 82 (12%) patients had HCT-specific comorbidity index of 3 or higher. There were 225 (34%) patients with PIF, 73 (11%) with early relapse, and 364 (55%) with late relapse. Reduced-intensity conditioning was administered to 462 (70%) patients. Regarding the donor type, 303 (46%) patients received related BM or PB, 120 (18%) received unrelated BM or PB, and 239 (36%) patients received unrelated cord blood. Regarding the primary endpoint, the 5-year PFS was 11.4% (95% CI, 9.1–14.0). In multivariable analysis, age 50 and above (HR, 1.19; 95% CI, 1.00–1.42; p = 0.047), male (HR, 1.26; 95% CI, 1.04–1.53; p = 0.020), and PS of 2 or higher (HR, 1.67; 95% CI, 1.39–2.00; p < 0.001) were identified as significantly negative prognostic factors for 5-year PFS, while relapsed over 12 months after autologous HCT (HR, 0.55; 95% CI, 0.42–0.73; p < 0.001) and male recipient with female donor (HR, 0.74; 95% CI, 0.60–0.93; p = 0.008) were identified as significantly positive prognostic factors for 5-year PFS. For the secondary endpoints, the 5-year OS, 5-year cumulative incidence of relapse/progression, and 5-year cumulative incidence of non-relapse mortality were 16.0% (95% CI, 13.3–19.0), 62.5% (95% CI, 58.7–66.1), 28.0% (95% CI, 24.5–31.6), respectively.

Conclusion

We demonstrated poor survival outcomes in patients with r/r DLBCL who underwent allogeneic HCT with SD or PD, with a 5-year PFS of 11.4%. Despite this, a subgroup of patients achieved a durable response after allogeneic HCT, potentially leading to a cure. We explored prognostic factors that may guide patients to benefit from allogeneic HCT.

Disclosures: Uchida: Astellas Pharma Inc.: Consultancy; Chugai Pharmaceutical Co.: Research Funding; Fuji Pharma Co.: Research Funding; Sumitomo Pharma Co.: Research Funding; Nippon Boehringer Ingelheim Co.: Research Funding; JCR Pharmaceuticals Co.: Research Funding; CSL Behring: Honoraria; MSD (Merck & Co. Inc.): Honoraria; Asahi Kasei Pharma Co.: Honoraria; Astellas Pharma Inc.: Honoraria; AstraZeneca: Honoraria; AbbVie GK: Honoraria; Otsuka Pharmaceutical Co.: Honoraria; Kyowa Kirin Co.: Honoraria; SymBio Pharmaceuticals: Honoraria; Daiichi Sankyo Co.: Honoraria; Takeda Pharmaceutical Co.: Honoraria; Chugai Pharmaceutical Co.: Honoraria; Nippon Shinyaku Co.: Honoraria; Takeda Pharmaceutical Co.: Consultancy; Novartis Pharma Co.: Honoraria. Yoshihara: Novartis Pharma K.K.: Honoraria; Janssen Pharmaceutical K.K.: Honoraria; Bristol-Myers Squibb Co: Honoraria; CHUGAI PHARMACEUTICAL Co., Ltd.: Research Funding. Serizawa: Sanofi K.K.: Honoraria; Janssen Pharmaceutical K.K.: Honoraria; Takeda Pharmaceutical Company Limited: Honoraria. Yoshimitsu: Sanofi: Honoraria; Takeda: Honoraria; Genmab: Honoraria; Daiichi Sankyo: Honoraria; Kissei: Honoraria; Bristol-Myers Squibb Company: Honoraria; Ono Pharmaceutical: Honoraria; Asteras: Honoraria; Meiji Seika Pharma Co., Ltd: Honoraria; Novartis: Honoraria; Chugai Pharmaceutical: Honoraria; Nippon Kayaku Co., Ltd.: Honoraria; PharmaEssentia Corp.: Honoraria. Kanda: Ono Pharma Inc.: Honoraria; Novartis Pharma K.K.: Consultancy, Honoraria; Janssen Pharmaceutical K.K.: Consultancy, Honoraria; Astellas Pharma Inc.: Consultancy, Honoraria; CSL Behring K.K.: 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; ASAHI KASEI PHARMA CORPORATION: Honoraria; Sanofi K.K.: Honoraria; asclepia: Honoraria; Kyowa Kirin Co., Ltd: Honoraria; NIPPON KAYAKU CO.,LTD.: Honoraria; MSD K.K.: Honoraria; DAIICHI SANKYO Co., Ltd.: Consultancy, Honoraria; Nippon Shinyaku Co., Ltd.: Honoraria; Sumitomo Dainippon Pharma Co., Ltd.: Honoraria; SymBio Pharmaceuticals, Ltd.: Consultancy; Megakaryon Co: Consultancy; AbbVie Inc.: Consultancy, Honoraria; Eisai: Research Funding.

*signifies non-member of ASH