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239 CD7 Chimeric Antigen Receptor T-Cell Therapy Bridging to Allogeneic Hematopoietic Stem Cell Transplantation Remarkably Improved Long-Term Disease-Free Survival in Refractory/Relapsed T-Cell Acute Lymphoblastic Leukemia/Lymphoma

Program: Oral and Poster Abstracts
Type: Oral
Session: 723. Allogeneic Transplantation: Long-Term Follow-Up and Disease Recurrence: Long-Term Survival and Survivorship From Clinical Trials And Observations
Hematology Disease Topics & Pathways:
Research, Lymphoid Leukemias, ALL, Biological therapies, Lymphomas, Clinical Research, Chimeric Antigen Receptor (CAR)-T Cell Therapies, T Cell lymphoma, Diseases, real-world evidence, Therapies, Lymphoid Malignancies, Transplantation
Saturday, December 9, 2023: 3:00 PM

Zhihui Li1*, Qinlong Zheng, MD2*, Keyan Yang2*, Teng Xu3*, Lei Wang1*, Xianxuan Wang1*, Xiaopei Wen1*, Yanzhi Song1*, Yongqiang Zhao1* and Tong Wu, MD4

1Department of Bone Marrow Transplantation, Beijing Gaobo Boren Hospital, Beijing, China
2Department of Medical Laboratory, Beijing Gaobo Boren Hospital, Beijing, China
3Department of Data Management, Beijing Gaobo Boren Hospital, Beijing, China
4Department of Bone Marrow Transplantation, Beijing Gobroad Boren Hospital, Beijing, China

Introduction: The prognosis of refractory/relapsed T-cell acute lymphoblastic leukemia/lymphoma (r/r T-ALL/LBL) is poor, and salvaged allogeneic hematopoietic stem cell transplantation (allo-HSCT) can only result in 20%-30% disease-free survival (DFS). Our previous clinical trials have shown that the patients with r/r T-ALL have achieved 90% complete remission (CR) with CD7 chimeric antigen receptor T cell (CART) therapy (Pan J. et al. JCO 2021), then quick received allo-HSCT to obtain 57% of 1-year DFS in 12 patients (Li ZH. et al. Transplantation and Cellular Therapy 2022).

Objectives: In current study, the long-term outcomes of allo-HSCT in r/r T-ALL/LBL after CD7 CART therapy in larger cohort are investigated, and compared with that chemotherapy only before allo-HSCT simultaneously. The risk factors for prognosis after allo-HSCT in this setting are also analyzed.

Methods: Between February 2018 and January 2023, total 90 patients with r/r T-ALL/LBL who underwent allo-HSCT in our hospital were included. The median age was 14 (2-65) years old. Somatic and germline gene mutations were detected by sequencing pre-transplant. Thirty-two (35.6%) patients were sensitive to chemotherapy and achieved CR before transplant (group A), and 58 (64.4%) cases were resistant to chemotherapy and in non-remission (NR) pre-HSCT. Forty-one of 58 patients in NR received CD7 CART before allo-HSCT (group B) and the rest 17 patients in NR underwent salvaged transplant (group C). Donor types included haploidential (60, 66.7%), unrelated (16, 17.8%) and identical sibling (14, 15.6%). Myeloablative conditioning regimens with either total body irradiation (TBI)/fludarabine (51, 56.7%) based or busulfan/fludarabine (39, 43.3%) based were applied. Antithymocyte globulin was used for haploidentical and unrelated transplants. Cyclosporine, mycophenolate mofetil and short-term methotrexate were employed for graft-versus-host disease (GVHD) prophylaxis.

Results: All patients achieved durable engraftment. No significant difference was found in the incidences of acute GVHD (aGVHD), chronic GVHD (cGVHD) and infections in 3 groups (p=0.612, p=0.091, p=0.649). With a median follow-up of 25.5 (19.6-32) months, 2-year overall survival (OS) in group B was similar to that in group A (54.4% vs. 69.9%, p=0.33) and much higher than that in group C (35.3%, p=0.0065), and 2-year DFS in group B was similar to that in group A (51.0% vs. 61.1%, p=0.24) and much higher than that in group C (17.6%, p=0.0029). No statistical difference was seen on transplant-related mortality (TRM) (17.3% vs. 9.8% vs. 11.8%, p=0.65) among group B, A, C. Two-year cumulative incidence of relapse in group B (31.7%) was similar to group A (29.0%), and much lower than that in group C (70.5%). The risk for relapse and death decreased remarkably in group B (p=0.0047) and group A (p=0.0003) compared with that in group C. NR before transplant (p=0.0062), aGVHD (p=0.013) and viral infections (p=0.047) were risk factors for relapse-related death, but TBI-based conditioning (p=0.01) was positive impact factor on OS. The most common somatic gene mutations were NOTCH1 (55.7%), JAK3 (18.0%), TP53 (16.4%), JAK1 (14.8%) and NRAS (14.8%). The most common germline gene mutations were EP300 (10.3%), ATM (8.6%), F7 (8.6%), KIT (8.6%) and NCF2 (8%). The patients with somatic TP53 or MED12 mutation had significantly higher risk for relapse and death (p=0.0018, p=0.0068). Germline gene mutations had no significant influence on prognosis post-transplant. Multivariate analysis had shown that CD7 CART (p=0.037), TBI-based conditioning (p=0.002) and cGVHD (p=0.004) were independent positive impact factors on OS, but aGVHD (p=0.034) and TP53 mutation (p=0.002) were independent negative impact factors for OS. Meanwhile, CD7 CART (p=0.005) and TBI-based conditioning (p=0.024) had positive impact on DFS, but TP53 mutation (p=0.02) also had negative impact on DFS.

Conclusions: Our study has demonstrated that CD7 CART followed by allo-HSCT has remarkably improved long-term DFS for chemotherapy-resistant T-ALL/LBL, and achieved comparable results in safety and efficacy with chemotherapy-sensitive disease post-transplant. Our study has also shown the profiles of somatic and germline gene mutations in r/r T-ALL/LBL, and identified some positive and negative impact factors for prognosis after transplant in this setting.

Disclosures: No relevant conflicts of interest to declare.

*signifies non-member of ASH