Novel therapeutics in the management of adult B-cell acute lymphoblastic leukemia
B-ALL is a rare malignancy, with approximately 6800 new cases diagnosed annually in the United States, and historically, long-term survival rates in adults ranged between 40–50%.[3]
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.
The decline in survival rates in adult B‑ALL historically reflects the limited effectiveness of conventional chemotherapy and the need for novel therapeutic strategies that can improve cure rates and reduce toxicity.
Evidence level: Állatkísérletes. Állatmodellben vizsgálták.
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