A systematic review and meta-analysis of CD-19-specific CAR-T cell therapy in relapsed/refractory acute lymphoblastic leukaemia in paediatrics and young adults: Safety and efficacy outcomes

ABSTRACT: Acute lymphoblastic leukaemia (ALL) typically responds better when treated with multiagent chemotherapy in paediatrics and young adolescents. Treatment of relapsed/refractory (RR) ALL remains a challenge. Even after stem cell transplantation (SCT) and intensive chemotherapy, the prognosis of relapsed/refractory ALL (RR ALL) remains grave. The advent of chimeric antigen receptors (CAR) has demonstrated promising results in RR ALL. Chimeric antigen receptor-T cells (CAR-T) and engineered T-cells are used to target cancer cells. In 2017, the FDA approved CD-19 specific CAR-T (tisagenlecleucel) for RR B-cell ALL in patients under 25 years old. In this systematic review, we will discuss the efficacy and safety of CD-19 specific CAR-T cell therapy in RR B-ALL in paediatrics and young adults. We searched the PubMed, Embase, Web of Science, Cochran’s library, and clinical trials databases. A total of 448 patients received a CD-19 specific CAR-T cell product, and 446 patients were evaluable. The age range was 0–30 years. The incidence rate of complete remission was 82%. The cumulative incidence of relapse after CD-19 CAR-T cell therapy is 36%. Similarly, the incidence rate of ≥ Grade 3 adverse events of neutropenia, thrombocytopenia, neurotoxicity, infections, and cytokine release syndrome were 38%, 23%, 18%, 29%, and 19%, respectively. Our subgroup analysis shows the incidence rate of minimal residual negative complete remission was 69% with the CD 28z co-stimulatory domain, 81% with the 41-BB domain, and 77% with fourth-generation CD-19 CAR-T cell therapy.