Application of immunotherapy in relapsed/refractory B-cell acute lymphoblastic leukemia / 中国药房

Immunotherapy， as an emerging treatment method， has been proven to improve the prognosis of patients with relapsed/refractory B-cell acute lymphoblastic leukemia （B-ALL） and has good application prospects. Immunotherapy， including chimeric antigen receptor T cell immunotherapy （CAR-T） and monoclonal antibodies， has shown great potential for application， and has been approved for marketing. This article summarizes the application of the above two therapies in the treatment of relapsed/ refractory B-ALL， and concludes that CAR-T is a kind of personalized immunotherapy， and the selection of ideal targets is an important part of its action. Currently， the ideal targets in clinical studies include CD19， CD22 and CD19/CD22. Monoclonal antibodies， including blinatumomab and inotuzumab ozogamicin， have shown superior therapeutic efficacy for relapsed/refractory B- ALL. Immunotherapy has shown superior therapeutic effects compared to conventional chemotherapy， expanding the selection of treatment options for relapsed/refractory B-ALL.

[CAR-T therapy for pediatric acute lymphoblastic leukemia].

The prognosis of B-cell acute lymphoblastic leukemia in children, adolescents, and young adults has improved significantly over the second half of the last century, with long-term survival rates reaching 90%, due to risk factor stratification and risk-adjusted treatment intensity. On the contrary, there are relapsed/refractory cases, and antibody-mediated immunotherapy and chimeric antigen receptor T-cell therapy are now being used in combination with conventional chemotherapy and allogeneic hematopoietic cell transplantation; the development of this treatment is expected. Tisagenlecleucel is extensively used in Japan and abroad because of its high complete remission rate in high-risk relapsed/refractory cases, including unresponsive to chemotherapy, relapsed after transplantation, and transplant-unsuitable cases. Several studies have been published in the last 2-3 years that discuss risk factors for relapse after tisagenlecleucel and the need for consolidative therapy. This manuscript presents the direction of these discussions and perspectives.

Efficacy and safety of CD19 CAR-T cell therapy for patients with B cell acute lymphoblastic leukemia involving extramedullary relapse.

OBJECTIVE: To evaluate the efficacy and safety of CD19 chimeric antigen receptor (CAR) T cell therapy for patients with B cell acute lymphoblastic leukemia (B-ALL) involving extramedullary relapse. METHODS: Fifteen patients with B-ALL involving extramedullary relapse who received CD19 CAR-T cell therapy in the First Affiliated Hospital, Zhejiang University School of Medicine from January 2016 to October 2021 were enrolled in this study. The overall survival and leukemia-free survival of patients were analyzed using Kaplan-Meier curves, and the response of extramedullary lesions in different locations following the CD19 CAR-T cell therapy was observed. Cytokine release syndrome (CRS), hematological toxicity, and immune effector cell-associated neurotoxicity syndrome (ICANS) during CD19 CAR-T cell therapy were analyzed. RESULTS: The median follow-up time was 7 (3-71) months, and 11 cases (73.3%) achieved complete response, median duration of complete response was 6 (2-27) months; 3 cases (20.0%) achieved partial response; 1 case (6.7%) got progressive disease. The overall response rate was 93.3% (14/15), and the overall survival rate was 80.0% (12/15) at the end of follow-up. The cumulative incidence of relapse was 40.0% (6/15) and relapse mortality rate was 20.0% (3/15). Until last follow-up date, 9 cases (60.0%) were still in disease-free survival. Among the 15 patients, 13 cases (86.7%) developed cytokine release syndrome (CRS) after cell infusion, including 7 cases with grade 1-2 CRS, 6 cases with grade 3 CRS; 1 case suffered from reversible ICANS; 15 cases (100.0%) developed B cell dysplasia; 12 cases (80.0%) developed severe hematologic adverse reactions; 2 cases (13.3%) had abnormal liver function; 1 case (6.7%) had abnormal renal function; 4 cases (26.7%) developed infection. The adverse reactions mentioned above were well controlled. CONCLUSION: CD19 CAR-T cell therapy shows explicit efficacy and controllable adverse reactions for B-ALL patients with extramedullary relapse.

Chimeric Antigen Receptor T-cell Therapy: Current Status and Clinical Outcomes in Pediatric Hematologic Malignancies.

Chimeric antigen receptor T-cell (CART) therapy has transformed the treatment paradigm for pediatric patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL), with complete remission rates in key pivotal CD19-CART trials ranging from 65% to 90%. Alongside this new therapy, new toxicity profiles and treatment limitations have emerged, necessitating toxicity consensus grading systems, cooperative group trials, and novel management approaches. This review highlights the results of key clinical trials of CART for pediatric hematologic malignancies, discusses the most common toxicities seen to date, and elucidates challenges, opportunities, and areas of active research to optimize this therapy.