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2818 Sequential CD19 and CD22 CAR-T Therapy in Relapsed/Refractory Acute Lymphoblastic Leukemia

Program: Oral and Poster Abstracts
Session: 613. Acute Lymphoblastic Leukemias: Therapies Excluding Allogeneic Transplantation: Poster II
Hematology Disease Topics & Pathways:
Research, Lymphoid Leukemias, ALL, Clinical Research, Diseases, Real-world evidence, Lymphoid Malignancies
Sunday, December 8, 2024, 6:00 PM-8:00 PM

Tingting Yang1,2,3*, Yetian Dong1,2,3*, Mingming Zhang2,3,4*, Jingjing Feng1,2,3*, Shan Fu2,3,5*, Pingnan Xiao1,2,3*, Ruimin Hong2,3,5*, Huijun Xu2,3,6*, Jiazhen Cui1,2,3*, Simao Huang1,2,3*, Guoqing Wei1,2,3*, Alex H. Chang7*, He Huang, MD1,2,8* and Yongxian Hu1,2,3*

1Bone Marrow Transplantation Center of The First Affiliated Hospital Liangzhu Laboratory, Zhejiang University School of Medicine, Hangzhou, China
2Institute of Hematology, Zhejiang University, Hangzhou, China
3Zhejiang Province Engineering Research Center for Stem Cell and Immunity Therapy, Hangzhou, China
4Bone Marrow Transplantation Center of The First Affiliated Hospital Liangzhu Laboratory, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
5Bone Marrow Transplantation Center, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
6Bone Marrow Transplantation Center of The First Affiliated Hospital & Liangzhu Laboratory, Zhejiang University School of Medicine, Hangzhou, China
7Shanghai YaKe Biotechnology Ltd, Shanghai, China
8Zhejiang Province Engineering Research Center for Stem Cell and Immunity Therapy, hangzhou, China

Background: Chimeric antigen receptor (CAR)-T cell therapy has shown promise in treating relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL). However, high relapse rates remain a significant challenge, and antigen-loss relapse is a common cause of treatment failure. Sequential targeting of CD19 and CD22 with CAR-T cells has emerged as a potential strategy to address this issue, although research in adult patients is relatively limited.

Methods: Our retrospective study evaluated the efficacy and safety of sequential CD19 and CD22 CAR-T cell therapy in adult patients with R/R B-ALL who were ineligible for allogeneic hematopoietic stem cell transplantation (allo-HSCT). Patients underwent CD19 CAR-T cell infusion followed by CD22 CAR-T cell infusion after at least one month. Key endpoints included minimal residual disease-negative complete remission (MRD-CR), overall survival (OS), leukemia-free survival (LFS), and safety outcomes.

Results: 23 participants were enrolled, with a median age of 58.1 years (range, 25.9 to 76.0). High-risk cytogenetic and genomic aberrations were detected in 13 (56.5%) patients, and 5 patients had extramedullary disease (EMD) involvement at baseline. Median interval between two CAR-T infusions was 3.8 months (range, 1.8 to 8.8). Hematological adverse events of grade 3 or worse occurred at similar rates after both CAR-T infusions. There were no treatment-related deaths. CRS occurred in 78.3% of patients following CD19 CAR-T therapy and 39.1% following CD22 CAR-T therapy. Two (8.7%) patients experienced grade 2 ICANS during CD19 CAR-T, and no ICANS was reported during CD22 CAR-T therapy. Infection rates were 30.4% during the first infusion and 26.1% during the second infusion, with all cases successfully resolved. Median peak CAR T-cell levels were significantly higher in the first cycle compared to the second cycle (353.2/μL vs 34.5/μL, P=0.002), suggesting a more robust initial expansion. Peak CD22 CAR-T cell levels were significantly lower in patients who relapsed (P=0.034), while peak CD19 CAR-T cell levels showed no significant difference between 2 groups (P=0.29).

With a median follow-up of 17.7 months, 65.2% of patients were alive, and 60.9% remained in MRD-CR. The median OS and LFS for the cohort were 25.4 months and 20.8 months, respectively. OS and LFS rates were 91.1% and 65.1% at 1 year, and 56.8% and 44.7% at 2 years. A total of 8 patients suffered leukemia relapse, with a median time from CD19 CAR-T of 8.5 months (range, 5.1 to 20.8). Relapse types included CD19+CD22+ (n=6, 75%), CD19-CD22+ (n=1, 12.5%), and CD19-CD22- (n=1,12.5%). The cumulative incidences of relapse were 30.5% at 1 year and 44.5% at 2 years. Multivariate analyses for OS and LFS confirmed that higher baseline leukemia burden (≥64%) and the presence of EMD were significant risk factors of inferior outcomes. Among patients with durable responses, 21.4% (3/14) maintained BCA longer than 6 months following CD22 CAR-T infusion. Of the 8 relapsed patients, loss of BCA preceding relapse was observed in 3 cases (37.5%), concurrent loss of BCA and relapse in 4 cases (50%), ongoing BCA in 1 case (12.5%).

Conclusion: Sequential CD19 and CD22 CAR-T cell therapy demonstrates durable efficacy and a manageable safety profile in relapsed/refractory B-ALL, providing a promising option to address antigen-loss relapse and improve long-term outcomes in patients ineligible for allo-HSCT.

Disclosures: No relevant conflicts of interest to declare.

*signifies non-member of ASH