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ICC 2023

Fan Yang

 Fan Yang, Speaker at Oncology Conference
Beijing Gobroad Boren Hospital, China
Title : Efficacy and toxicity for CD7 chimeric antigen receptor T- Cell therapy in patients with relapsed/refractory T- Cell lymphoma


Background: The prognosis of refractory/relapsed T-cell lymphoma is extremely poor, especially for the patients who failed to allogeneic hematopoietic stem cell transplantation(alloHSCT).

Aims: The aim was to assess humanize CD7 chimeric antigen receptor (CAR) T-cell safety and efficacy in patients with r/r T-cell lymphoma.

Methods: From August 2017 to December 2022, 20 patients were enrolled. The median age was35 (18-72) years old. The diagnosis included T cell lymphoblastic leukemia/lymphoma(T-LBL) (n=17) ?hepatosplenic T-cell lymphoma(HSTL,n=1)?monomorphic epitheliotropic intestinal T-cell lymphoma(MEITL,n=1) and cutaneous T-cell lymphoma( CTCL?n=1).The disease status was progressive disease (PD)in all patients who failed to multi-line therapies, including autologous HSCT (n=5), and alloHSCT(n=9).Six patients(6/20, 30%)had central nervous system involvement.In order to further reduce the tumor burden, 8/20(40%) patients were treated with bridging therapy before CAR-T cell infusion. Before the trial, the expression of CD7 antigen in tumor tissue was positive confirmed by pathology. Infusion of donor-derived CD7 CAR-T cells in patients who have relapsed after alloHSCT, whereas infusion of autologous CAR-T cells in other patients.Patients received fludarabine and cyclophosphamide regimens before CAR-T cell infusion. The kinetics and function of CAR-T cells was monitored by quantitative PCR and flow cytometry. The efficacy was evaluated by PET-CT as well as bone marrow puncture after CAR-T infusion.

Results: The median CAR-T cells infused were 1×105/kg (range,0.06-34×105/kg ). For CAR T cell expansion,the peak time in vivo was on median 14(range,11-29) days after CAR-T cell infusion.The median peak kinetics of CAR-T cells in peripheral blood of individual patients measured by flow cytometry was 23.65(range,1.61-49)×106/L, which was no correlation with the number of CAR-T infused(P=0.0818) .Peak CAR-T amplification is also independent of whether CART cells are sufficiently donor-derived(P=0.4692). Levels of CAR-T cells were very low after the first 1 months postinfusion. The incidence of grade 3 cytokine release syndrome (CRS) was 15% (3/20), and the incidence of grade 1-2 neurotoxicity was 10% (2/20).Although CD7-positive normal T cells were depleted, CD7-negative T cells expanded in all patients.Seventeen patients had occurred cytopenias. Nine patients?9/20,45%?had prolonged cytopenias (1 month).Viremia occurred in 12/20(60%)patients. 2/20(10%) patient developed post transplant lymphoproliferative disorders(PTLD)associated with EBV infection.1/9(11%) patients after allogeneic HSCT were found to have grade IV aGVHD (intestinal) .

 Conclusion: Our study showed promising efficacy of CD7 CAR-T cell therapy in r/r T-cell lymphoma. CRS is       manageable.For patients who have relapsed after allogeneic transplantation, bridge second transplantation is       recommended if CD7 CAR-T therapy is effective