Bispecific T-Cell Engager Therapy in Relapsed Acute Lymphoblastic Leukemia: A Review of Published Cohorts

Abstract

A bispecific antibody that redirects the patient's own T cells against CD19 doubled complete remission rates against chemotherapy in relapsed disease. The more useful finding is buried in the burden data: the same agent clears residual disease in four fifths of patients but produces remission in fewer than half of those with overt marrow involvement. Objectives: To review the published evidence on bispecific T-cell engager therapy in relapsed and refractory B-cell precursor acute lymphoblastic leukaemia: what the randomised comparison established, how response varies with disease burden, what is achieved in the molecular disease setting, what toxicity occurs in routine use, and how the agent should be sequenced. Material and Methods: Narrative review of randomised trials, single-arm registration studies, real-world multicentre series and regulatory assessments indexed in PubMed and the major haematology journals. Studies were eligible if they reported efficacy or toxicity of bispecific T-cell engager therapy in a defined B-cell
precursor 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 randomised comparison against standard-of-care chemotherapy in Philadelphia-negative relapsed or refractory disease, median overall survival was 7.7 against 4.0 months (HR 0.71, p = 0.012) and complete remission 34 against 16 per cent. In Philadelphia-positive disease, a single-arm study reported complete remission in 31 per cent. An earlier phase II study achieved complete remission or complete remission with partial haematological recovery in 43 per cent after two cycles, with median relapse-free survival of 5.9 months and overall survival of 6.1 months. Where only molecular disease remained, 16 of 21 patients cleared residual disease, 12 of those having been molecularly refractory to prior chemotherapy, with relapse-free survival of 78 per cent at a median follow-up of 405 days. Across 39 children and adolescents treated in routine practice, complete remission reached 46 per cent among those with 5 per cent or more blasts against 81 per cent residual disease clearance among those below that threshold, with grade 3 or higher events in 34.8 per cent, no cytokine release syndrome and no toxic deaths. Conclusion: Efficacy scales inversely with disease burden, and the licensed indication describes the setting in which the agent performs least well. Median survival of 7.7 months in overt relapse is a real improvement over 4.0 and remains under a year.
Abbreviations: ALL – Acute Lymphoblastic Leukaemia, BCP-ALL – B-Cell Precursor ALL, BiTE – Bispecific T-Cell Engager, R/R – Relapsed or Refractory, Ph – Philadelphia Chromosome, CR – Complete Remission, CRh – Complete Remission with Partial Haematological Recovery, MRD – Measurable Residual Disease, RFS – Relapse-Free Survival, OS – Overall Survival, CRS – Cytokine Release Syndrome, allo-HSCT – Allogeneic Haematopoietic Stem Cell Transplantation, CAR – Chimeric Antigen Receptor.