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2100 Prophylactic or Preemptive Donor-Derived CD19 CAR-T Cell Infusion for Preventing Relapse in High-Risk B-ALL after Allogeneic Hematopoietic Stem Cell TransplantationClinically Relevant Abstract

Program: Oral and Poster Abstracts
Session: 704. Cellular Immunotherapies: Early Phase and Investigational Therapies: Poster I
Hematology Disease Topics & Pathways:
Lymphoid Leukemias, ALL, Biological therapies, Clinical Practice (Health Services and Quality), Chimeric Antigen Receptor (CAR)-T Cell Therapies, Diseases, Therapies, Lymphoid Malignancies
Saturday, December 9, 2023, 5:30 PM-7:30 PM

Wenyi Lu, PhD1,2*, Meng Zhang2*, Hairong Lv2*, Xia Xiao, MD2*, Xue Bai2*, Jiaxi Wang2*, Yedi Pu2*, Juanxia Meng2*, Xiaomei Zhang3*, Haibo Zhu2*, Ting Yuan2*, Bing Wang2*, Xin Jin, MD2*, Xinping Cao2*, Zhao Wang2*, Tianle Xie2*, Haotian Meng2*, Alexey Stepanov4*, Alexander G. Gabibov5*, Yuxin An, MD2*, Rui Sun3*, Yu Zhang2*, Mikhail A. Maschan6*, Zunmin Zhu, MD, PhD7*, Hongkai Zhang8* and Mingfeng Zhao2

1Henan Provincial People’s Hospital, Zhengzhou, China
2Tianjin First Central Hospital, Tianjin, China
3Medical School of Nankai University, Tianjin, China
4M.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Moscow, Russia, Moscow, RUS
5M.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry of the Ru, Moscow, RUS
6Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology, and Immunology, Moscow, Russia, Moscow, Russian Federation
7Department of Hematology, Henan Provincial People’s Hospital, Zhengzhou, China
8State Key Laboratory of Medicinal Chemical Biology and College of Life Science,, Tianjin, CHN

Introduction: Relapse remains a significant challenge in the management of high-risk B-cell acute lymphoblastic leukemia (B-ALL) patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). Existing post-transplant relapse prevention strategies for high-risk B-ALL patients after transplantation, particularly in cases of Philadelphia chromosome-negative B-ALL, have limitations and suboptimal efficacy. This study aims to evaluate the efficacy and safety profile of prophylactic or preemptive infusion of donor-derived CD19 chimeric antigen receptor T (CAR-T) cells in high-risk B-ALL patients after allo-HSCT.

Methods: Between May 2017 and July 2022, high-risk B-ALL patients with minimal residual disease (MRD) positive or MRD negative status after allo-HSCT were enrolled in clinical trials of donor-derived CD19 CAR-T cell therapy (ChiCTR 2000041025 and ChiCTR-ONN-16009862). The primary outcome was the cumulative incidence of relapse (CIR). Secondary outcomes were progression-free survival (PFS), overall survival (OS) and CAR-T cell treatment-related toxicities.

Results: A total of 25 high-risk B-ALL patients who received infusion of donor-derived CD19 CAR-T cells after allo-HSCT were enrolled in the CAR-T cell group, including 8 patients with MRD and 17 patients without MRD. A contemporaneous cohort of 43 high-risk B-ALL patients who did not receive CAR-T cell therapy in MRD-positive or MRD-negative status after transplantation was also included as a control group. The median age of patients enrolled in the CAR-T group was 29 years (range: 9-60 years). The median infused CAR-T cell dose was 2.5×10^6/kg (range: 1.0-5.0×10^6/kg), with a median time from transplantation to CAR-T cell treatment of 122 days (range: 45-315 days). The median follow-up duration was 23.6 months (range: 8.3-60.6 months). Of the 25 patients in CAR-T group, eight MRD-positive patients achieved MRD-negative remission after CAR-T cells treatment (Figure1A). The two-year cumulative incidence of relapse in the CAR-T cell group was significantly lower at 4.8% (95% CI: 0.0%-12.6%) compared to the control group's incidence of 26.6% (95% CI: 11.4%-41.8%, P = 0.03,Figure1B). Additionally, the CAR-T cell group exhibited a higher two-year PFS rate [86.3% (95% CI: 71.8%-100%)] compared to the control group [63.5% (95% CI: 48.0%-79.0%), P = 0.04]. However, the two-year OS rates were comparable between the CAR-T cell group [91.0% (95% CI: 79.0%-100%)] and the control group [79.1% (95% CI: 66.0%-92.2%), P = 0.20]. Adverse events were well tolerated, and no patients experienced grade 3-4 cytokine release syndrome or any grade of immune effector cell-associated neurotoxicity syndrome. Hematological cytopenia was the most severe CAR-T cell related toxicity, but the toxicity was manageable, and only three patients experienced acute graft-versus-host disease following CAR-T cell infusion.

Conclusions: Prophylactic or preemptive infusion of CAR-T cells after allo-HSCT demonstrated a reduced incidence of relapse and acceptable adverse events in high-risk B-ALL patients. These findings highlight the potential of CAR-T cell therapy as a promising strategy for relapse prevention in high-risk B-ALL patients after allo-HSCT.

Disclosures: No relevant conflicts of interest to declare.

*signifies non-member of ASH