Should immunologic strategies be incorporated into frontline ALL therapy?

Survival rates in adult patients with acute lymphoblastic leukemia (ALL) have markedly improved during the past decade. The one-size-fits-all-ages approach has been replaced with adaptation of pediatric-inspired treatment protocols for younger adults. Yet different treatment strategies for older patients are needed due to chemotherapy-related toxicities. A new era of immunotherapy has arrived, offering opportunities for targeted treatments for ALL subtypes. While CD20 targeting with rituximab has been demonstrated to improve survival when combined with chemotherapy, it has little activity as a single agent in ALL. In contrast, antibody targeting of CD19 and CD22 with blinatumomab and inotuzumab ozogamicin, respectively, has had remarkable single-agent activity in the relapsed setting. Studies are now underway to test these agents in combination with chemotherapy in the frontline setting. The goal of these studies is to improve event-free survival and overall survival by using these approaches in the frontline to eradicate minimal residual disease and, particularly in older adults with ALL, to reduce treatment-related toxicity by limiting the exposure to traditional multi-agent chemotherapy with its attendant toxicities. This review focuses on new immunotherapeutic treatment options and strategies for frontline treatment, including a brief discussion of the use of true immunotherapy, chimeric antigen receptor T-cells, for relapsed B-cell ALL, the potential for targeting CD38 in T-cell ALL, and how these approaches are facilitating the next steps to improve survival for adult patients with ALL.