Adult acute lymphoblastic leukemia: incorporation of recent advances into current treatment strategies

Outcomes in B-cell acute lymphoblastic leukemia (ALL) have improved over time due to therapeutic advances, and improved disease monitoring and prognostication. The BCR::ABL1 tyrosine kinase inhibitors (TKIs) were the first targeted therapies to significantly impact the therapeutic trajectory and outcomes of Philadelphia chromosome-positive (Ph-positive) ALL. Similarly, antibodies targeting CD19/20/22 and engineered chimeric antigen receptor (CAR) T-cell immunotherapies have drastically changed the therapeutic landscape and outcomes of B-cell ALL. Incorporation of the bispecific T-cell engager (BiTE) blinatumomab has demonstrated a significant survival advantage in patients with both newly diagnosed Philadelphia chromosome-negative (Ph-negative) and Ph-positive ALL. Inotuzumab ozogamicin, the anti-CD22 antibody drug conjugate (ADC), has also been safely integrated into the frontline treatment backbones in both younger and older patients. CAR T-cell therapy has resulted in durable remissions in relapsed/refractory (R/R) ALL, especially with lower disease burden. CAR T-cell therapy consolidation in the frontline setting is being pursued with the goal of reducing the need for allogeneic stem cell transplantation (alloSCT). Future research is focusing on treatment optimization through replacement of chemotherapy with immunotherapies with the goal of reducing toxicities, minimizing the need for alloSCT, and shortening the intensity and duration of therapy while improving long-term outcomes.