From April 14 to 17, 2024, the 50th Annual Congress of the European Society for Blood and Marrow Transplantation (EBMT) was held with great ceremony in Glasgow, UK. The conference focused on the latest advancements in stem cell transplantation and cell therapy, advancing patients with hematological diseases towards better clinical prognoses. At this congress, Dr. Li Gao from Soochow University Affiliated Children’s Hospital reported on a study.
Background: Childhood relapsed/refractory acute lymphoblastic leukemia (ALL) is a life-threatening condition with poor treatment outcomes. CAR-T cell therapy has emerged as a promising treatment strategy in this setting. However, the factors affecting the efficacy of CAR-T treatment are still unclear. We presented the single-center results of CAR-T cell therapy in children with first relapse or refractory B-ALL and attempted to explore the factors that influence the prognosis of CAR-T treatment.
Methods: Children with first relapsed or refractory B-ALL who received CAR-T cell therapy at our center between 03/2017 and 08/2023 were included in this study. The CAR-T cells were generated using CD19- or CD19/CD22- targeting CAR constructs and administered to patients following lymphodepleting chemotherapy. A total of 130 patients were included in this study, of which 21 received CD19 CAR-T cells and 109 received CD19/CD22 CAR-T cells. Bone marrow assessments were carried out on day 7 following CAR-T cell infusion, and the lymphocyte subsets and bone marrow results at 1 month, 3 months, and 6 months were collected for analysis. The primary objective of this study was to assess the efficacy and safety of CAR-T cell therapy. The secondary objectives included evaluating the event-free survival, overall survival, and potential prognostic factors.
Results: The median age at CAR-T cell therapy was 4.2 years (range: 1-14.7) and 67.7% were males. The complete remission (CR) of measurable residual disease (MRD) negative rates were 70.0% in the CD19 CAR-T cell group, and 94.9 % in the CD19/CD22 CAR-T cell group respectively. The CD19/CD22 CAR-T cell group demonstrated a significantly higher CR rate compared to the CD19 CAR-T cell group (P<0.05). The most common adverse events included cytokine release syndrome (89.9%), and 36.4% were grade 3 or higher. The estimated overall survival at 2 years was 67.8% and EFS 54.2%. The CD19/CD22 CAR-T cell group showed a significantly higher OS and EFS compared to the CD19 CAR-T cell group (P<0.05). Improved event-free survival with bridging transplantation following CAR-T cell therapy was observed. Multivariate analysis of CD19/CD22 CAR-T without bridging transplantation revealed that MRD positivity at day 7 after CAR-T cell infusion was an independent adverse prognostic factor for OS (hazard ratio [HR]: 6.300, P=0.022). Additionally, higher CD4 counts at 1-month post-infusion were independently associated with better EFS (HR: 0.165, P =0 .021).
Conclusions: CD19/CD22 CAR-T cell therapy may provide superior efficacy compared to CD19 CAR-T cell therapy in children with first relapse or refractory B-ALL. The dual-targeting approach may enhance the depth of remission and survival. Patients may not need bridging transplantation if they achieve negative MRD on day 7 and have a higher CD4 count one month after CD19/CD22 dual-target CAR-T therapy.
Commentary
I reported on behalf of our team regarding the efficacy analysis of CAR-T therapy for children with relapsed or refractory acute lymphoblastic leukemia (ALL) in a single-center study, as well as an exploration of factors that influence treatment outcomes.The results of our study showed that ORR, overall survival (OS), and event-free survival (EFS) of dual-target CAR-T for CD19/CD22 were significantly better than those of single-target CAR-T for CD19. In patients who did not undergo hematopoietic stem cell transplantation after receiving dual-target CAR-T for CD19/CD22, we found that minimal residual disease (MRD) negativity on the 7th day after CAR-T infusion and the CD4 count at one month were independent risk factors affecting the prognosis of CAR-T therapy.
