Innovative Approaches to the Management of Acute Lymphoblastic Leukemia Across the Age Spectrum

Adults compose nearly half of all patients diagnosed with acute lymphoblastic leukemia (ALL) and historically have had poor survival compared with pediatric patients. Recently approved therapies, such as monoclonal antibodies, CAR T-cell constructs, and next-generation tyrosine kinase inhibitors, have improved survival in relapsed and refractory ALL, and studies are now examining incorporating these treatments and others into the upfront setting. In adolescent and young adult patients, use of pediatric-based regimens has already improved survival compared with historical controls, and the addition of monoclonal antibodies, such as inotuzumab ozogamicin and blinatumomab, may further enhance this survival benefit. In older adults, approaches have centered on minimizing conventional chemotherapy to decrease toxicity by incorporating monoclonal antibodies and other novel therapies to increase efficacy. With the addition of tyrosine kinase inhibitors to chemotherapy for patients with Philadelphia chromosome-positive ALL, survival of this once poor-prognosis ALL subtype now approaches or exceeds outcomes of other subtypes of adult ALL. Further refinements in the backbone treatment regimen and optimal consolidation approaches will likely improve survival further. Although allogeneic hematopoietic stem cell transplant was previously routinely used as consolidation for adults with ALL, incorporation of measurable residual disease and other risk stratification strategies has enabled better identification of patients who will benefit from allogeneic hematopoietic stem cell transplant. Ongoing clinical trials investigating these approaches will continue the evolution of treatment approaches for adults with ALL, with further improvement in outcomes anticipated.