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3467 The Safety and Efficacy of CD33 CAR-T Therapy for RR AML after HSCT

Program: Oral and Poster Abstracts
Session: 704. Cellular Immunotherapies: Early Phase Clinical Trials and Toxicities: Poster II
Hematology Disease Topics & Pathways:
Clinical Practice (Health Services and Quality), Diseases, Adverse Events, Myeloid Malignancies
Sunday, December 8, 2024, 6:00 PM-8:00 PM

Yuehui Lin1*, Defeng Zhao2*, Biping Deng, BS, MD3*, Dan Liu4*, Hong Yan, Bachelor of Medicine5*, Biyi Li, Master of Medical Science5*, Yu Xia6*, Ruyue Zheng, Master of Medical Science5*, Tong Wu, MD7,8 and Chunrong Tong4*

1Department of Haematology, Beijing Gobroad Boren Hospital, Beijing, China
2Beijing Gobroad Boren Hospital, Beijing,China, AL, China
3Department of Cytology Laboratory, Beijing Gobroad Boren Hospital, Beijing, China
4Beijing Gobroad Boren Hospital, Beijing, China
5Beijing Boren Hospital, Beijing, China
6Beijing Gobroad Boren Hospital, Department of Cytology Laboratory, China, Beijing, China
7Department of Bone Marrow Transplantation, Beijing GoBroad Boren Hospital, Beijing, China
8Beijing Boren Hospital, Langfang, Hebei, CHN

IntroductionAcute myeloid leukemia(AML) is a heterogeneous diseasea,although the prognosis has been significantly improved with the advancement of chemotherapy and targeted drugs, it still had no a safe and effective treatment for relapsed and refractory(R/R) AML,especially after allogeneic hematopoietic stem cell transplantation(allo-HSCT). Recently chimeric antigen receptor (CAR) T-cell therapy has developed rapidly on lymphoid tumors, but CAR-T cell therapy for AML still remains unsatisfactory. So, we conducted an exploration of humanized CD33 CAR-T(hCD33 CAR-T cell therapy for R/R AML after allo-HSCT.

MethodsA total of 12 patients who received hCD33 CAR-T treatment from May 8, 2023 to March 14, 2024 were included. The leukemia cells of all patients expressed CD33 before treatment and after excluding contraindications to CAR-T cell therapy, chemotherapy based on fludarabine was given as a pre-treatment regimen, then transfused hCD33 CAR-T cells collected from the donor or the patients with 6.2 × 104/kg6.15 × 105/kg. To observe the safety and efficacy after 15-30 days of CAR-T cell refusion by bone marrow(BM and cerebrospinal fluid CSFexamination.

Results12pts:3 females and 9 males with a median age of 36 years (1451 years). 1 pts relapsed after a second allo-HSCT, another 11 pts relapsed after a first allo-HSCT; 1 pts diagnosed APL, 1 pts diagnosed MDS to AML after HSCT, 10 pts were primary AML. Before CAR-T refused, 8 pts presented with 5.0% 85.5% leukemia blasts in BM/peripheral blood(PB) and 4 pts were minimal residual disease (MRD) – positived by Flow cytometry or Real time quantitative PCR for fusion gene(FCM+/FG+), 4 pts had central nervous system leukemiaCSF+. After CD33 CAR-T treatment, 5 (5/12, 41.67%) pts achieved BM complete remission (CR)(1 was MRD+CR, 4 was MRD- (FCM/FG)),;4 CSF+ pts:1 pts FG-MRD-of CSF, 1 pts FCM-MRD-, 1 pts MRD of CSF became negative before CAR-T refused and the other 1 pts were not examined. ALL of 12 pts, 2 pts were ineffective with no CRS response, and 1 of them had liver function damage suspected to be related to infection or leukemia; 9 pts had CRS 1, 1 pts had CRS 2, and no ICANS occurred in all patients; 4 pts experienced liver function damage after CAR-T cell transfusion, which may be related to GVHD or CRS; 2 pts effectively developed sepsis, 1 pts died from septic shock due to long-term granulocyte deficiency, and 1 pts was controlled after anti infective treatment. Follow up until June 20244m1y),1 pts were CMR without bridging a second allo-HSCT5 pts survived bridging a second allo-HSCTanother 6 pts were died due to infection or disease progression.

ConclusionsAs a salvage treatment for rr AML including those who relapse after allo-HSCT,our hCD33 CAR-T resulted in CR rate of 41.67% which already was better than other treatment such as chemotherapy,donor lymphocyte reinfusion DLIeven other CAR-Ts On the other hand, our experience , although we recommend patients to bridging secondary transplantation or donor stem cell reinfusion to support hematopoiesis after CD33 CAR-T, but actually CD33 CAR-T side effects can be controlled, and some patients can survive without bridging the secondary transplantation. So for rr AML patients even after allo-HSCT, CD33 CAR-T is still recommended.

Disclosures: No relevant conflicts of interest to declare.

*signifies non-member of ASH