CD7 CAR-T Therapy Followed by a Second Transplant for T-Cell Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma Patients Who Relapsed after a Prior Transplant
Blood（2023）
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Background,The therapeutic options for patients with T-cell acute lymphoblastic leukemia or lymphoblastic lymphoma (T-ALL/LBL) who relapse after hematopoietic stem cell transplantation (HSCT) are currently restricted. CD7-targeted chimeric antigen receptor (CAR) T-cell therapy provides a promising avenue towards remission yet the long-term prognosis for these patients still needs to be improved. The advantages of progressing to a second transplant post CAR-T treatment remain uncertain due to limited data. In this study we analyzed the clinical characteristics and transplantation outcomes of 16 TALL/LBL,patients who having relapsed after their initial transplantation achieved complete remission (CR) in bone marrow (BM) and CR/partial remission (PR) in extramedullary lesions via CD7 CAR-T therapy and then opted for a second allogeneic HSCT (allo-HSCT) at our center. Our aim is to explore strategies to enhance the survival rate of these patients.,Methods,From January 2021 to January 2023 we analyzed T-ALL/LBL patients who underwent second transplantation at Hebei Yanda Lu Daopei Hospital. The patients included in this study met the following criteria: they had relapsed following their first HSCT and had subsequently undergone CD7 CAR-T therapy prior to the second transplantation. The follow-up cut-off date was till June 1 2023. The median follow-up duration after the second transplantation was 178 days ranging from 9 to 500 days.,Results,A total of 16 patients including 13 with T-ALL and 3 with T-LBL were enrolled. There were 14 males and 2 females. The donor of first transplantation was autologous( n=3) sibling identical(n=2),unrelated donor(n=2) or haplo-identical (n=9). After the first transplantation 8 patients relapsed in bone marrow (BM) and 8 relapsed both in BM and extramedullary sites. Of these 13 patients received autologous CD7 CAR-T one patient received donor-derived CD7 CAR-T and one patient was treated with universal CAR-T cells. After the CD7 CAR-T therapy all 16 patients (100%) achieved minimal residual disease (MRD)-negative CR in BM and 6 out of 8 patients (75%) achieved CR in,extramedullary lesions. Only two patients exhibited PR in the extramedullary lesions.,The median age at the time of the second transplantation was 28 years (range 14-42 years). The median time from diagnosis to the second transplantation was 683 days (range 385-2672 days). The median interval between the first and second transplantation was 438 days (range 229-2540 days),and the median interval from CD7 CAR-T infusion to the second transplantation was 72 days (range 31-92 days).,For the second transplantation 13 cases had haplo-identical donors and 3 cases had unrelated donors. The conditioning regimens utilized were either total body irradiation (TBI)-based (n=9),busulfan-based (n=6) or melphalan-based (n=1). Following the 2 nd transplant the 1-year overall survival(OS) and leukemia-free survival(LFS) were 58.5% (95% CI 28.9-85.0%) and 51.4% (95% CI,22.4-79.9%) respectively(Figure 1). The 1-year relapse incidence (RI) and non-relapse mortality (NRM) were 15.9% ( 95% CI 4.4-57.8%) and 31.5% (95% CI 13.2-74.9%) respectively. The,cumulative incidence of CMV and EBV viremia at day 100 were 75.0% (95% CI 56.599.5%),and 19.8% (95% CI 7.2-54.6%) respectively. The cumulative incidence of all grades acute graft-versus-host disease (aGVHD) and 3-4 grade aGVHD at day 100 were 56.3% (95%CI 36.5-86.7%) and 25% (95%CI 10.7-58.4%) respectively. One-year chronic GVHD( cGVHD) was observed in 25.1% of the cases (95%CI 9.3-67.4%) while moderate to severe cGVHD was not found in any patient. Following the 2 nd transplant a total of 6 patients died including 3 from infection 2 from relapse and 1 from intracranial hemorrhage.,Conclusions,Our initial findings suggest that even in refractory/relapsed T-ALL/LBL patients who have,experienced relapse following previous HSCT MRD-negative complete remission can potentially be achieved utilizing CD7 CAR-T cell therapy. The subsequent implementation of a second allo-HSCT appears feasible. Combining CAR-T therapy with a follow-up second HSCT presents a strategy for these heavily pre-treated patients offering promising prospects for survival. However further evaluation of this treatment approach is required necessitating long-term monitoring and a larger patient cohort.
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