CAR T-Cell Therapy Outcomes and Toxicity Profiles in Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia

Abstract

CD19-directed CAR T-cell therapy induces remission in around four out of five children with relapsed or refractory B-cell leukaemia, all of them residual disease negative. Two years later, roughly a third have relapsed or died. The problem in this disease has moved from achieving remission to keeping it. Objectives: To review the published evidence on CD19-directed CAR T-cell therapy in relapsed or refractory B-cell acute lymphoblastic leukaemia: what remission rates are achieved, how durable those remissions are, what toxicities occur and at what severity, and why the available products are difficult to compare. Material and Methods: Narrative review of registration trials, extended follow-up analyses, registry cohorts and toxicity grading consensus documents indexed in PubMed and the major haematology journals. Studies were eligible if they reported efficacy or toxicity outcomes for CD19-directed CAR T-cell therapy in a defined B-cell acute lymphoblastic leukaemia population. No new patient data were generated and no patients were recruited; every estimate quoted is one published by the original investigators. Results: In the paediatric and young adult registration trial, overall remission within three months was 81 per cent among 75 evaluable infused patients, and every responder was residual disease negative by flow cytometry. Relapse-free survival at 18 months was 66 per cent (95% CI 52-77) and overall survival 70 per cent (95% CI 58-79), falling to 63 per cent at three years with a remission rate of 82 per cent on extended follow-up. Cytokine release syndrome affected 77 per cent of patients with 48 per cent grade 3 or 4 on the Penn scale, all reversible, and grade 3 neurological events occurred in 13 per cent. Of 25 post-infusion deaths, 2 occurred within 30 days and 23 later. In the adult trial, 55 infused patients achieved 71 per cent remission with durable remission in 48 per cent at one year, and grade 3 to 4 cytokine release syndrome and neurotoxicity occurred in 24 and 25 per cent respectively. Conclusion: Remission rates are high and residual disease negativity near universal among responders, but a third of patients are dead within three years and most deaths occur well beyond the acute toxicity window. The two licensed products were graded on different scales, so their toxicity figures cannot be compared directly. Abbreviations: ALL – Acute Lymphoblastic Leukaemia, B-ALL – B-Cell Acute Lymphoblastic Leukaemia, CAR – Chimeric Antigen Receptor, R/R –
Relapsed or Refractory, CRS – Cytokine Release Syndrome, ICANS – Immune Effector Cell-Associated Neurotoxicity Syndrome, ORR – Overall Remission Rate, MRD – Minimal Residual Disease, RFS – Relapse-Free Survival, OS – Overall Survival, HSCT – Haematopoietic Stem Cell Transplantation, scFv – Single-Chain Variable Fragment.