How should we treat older adults with Ph+ adult ALL and what novel approaches are being investigated?

Treatment of older patients with Philadelphia-chromosome-positive (Ph+) acute lymphoblastic leukemia presents unique challenges. Advanced age, comorbidities, high treatment-related death rates with traditional chemotherapy, and relapse combine to yield poor survival. Reduced-intensity induction with BCR-ABL1 targeted tyrosine kinase inhibitors (TKIs) and corticosteroids yields CR rates 96-100% with no induction mortality but relapse is nearly certain without effective consolidation. Few clinical trials provide guidance on optimal consolidation for older Ph+ ALL. With second-generation TKIs, lower intensity chemotherapy after induction gives similar outcomes to intensive consolidation although long-term survival is still poor. Consolidation with allogeneic or autologous hematopoietic cell transplantation may improve survival for fit older patients. Novel targeted therapies like blinatumomab, inotuzumab ozogamicin, and CD19-targeted CAR T-cells hold promise to improve survival with reduced toxicity. Better understanding these approaches will require increased referral to specialized centers, expansion of clinical trials, and improved enrollment of older ALL patients on trials.