Tamer Othman, Ibrahim Aldoss
Relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL) has historically been associated with poor outcomes in adults treated with conventional chemotherapy. Allogeneic hematopoietic cell transplantation (HCT) in second remission has been the only strategy associated with durable remissions and potential cure. However, achieving remission after first relapse was challenging in the era predating immunotherapy, and remissions were often brief, frequently limiting the ability to proceed to HCT. Consequently, for decades there has been a critical need for more effective therapeutic approaches in R/R B-ALL. Fortunately, in the last decade, B-ALL has undergone a remarkable therapeutic transformation with the introduction of novel targeted immunotherapies. Blinatumomab, inotuzumab ozogamicin, and chimeric antigen receptor (CAR) T-cell therapy have substantially improved patient outcomes in the R/R disease settings while reducing reliance on intensive cytotoxic chemotherapy, and their use has increasingly expanded into the frontline setting as well. This literature review summarizes the pivotal clinical trials supporting the use of blinatumomab, inotuzumab ozogamicin, and CAR T-cell therapies in B-ALL, with a particular focus on their efficacy and toxicity profiles. We also provide our perspective on how these agents can be incorporated into clinical practice and highlight emerging therapeutic agents and strategies. In conclusion, continued advancement and earlier integration of immunotherapeutic approaches could improve long-term outcomes in patients with B-ALL.