Immune targeting in Ph-negative and Ph-positive B-ALL: improving outcomes and minimizing chemotherapy in adult B-ALL

With the addition of antibody-based immunotherapy to frontline treatment regimens for B-lineage acute lymphoblastic leukemia (B-ALL), patients across the age spectrum now experience superior long-term survival. The pressing question for the field is whether immunotherapy may replace some of the intensive elements of the standard chemotherapy backbone to reduce overall toxicity and duration while maintaining superior outcomes. For young adults with B-ALL, most clinical trials have added immunotherapy to the intensive, pediatric-inspired regimens to achieve deeper remissions, while necessarily increasing duration, complexity, and possible toxicities. In contrast, clinical trials for older adults have used immunotherapy as a substitute to eliminate or reduce cytotoxic chemotherapy. And although survival outcomes for older adults remain distinctly inferior to those in the pediatric age group, it is hoped that the potential simplification of the chemoimmunotherapy backbone for all patients may be guided by the successes and shortcomings discovered in the treatment of older adults. In this article, I discuss the treatment of older adult patients with B-ALL in the immunotherapy era and how this approach may pave the way for implementing a deescalation strategy for younger adult patients with B-ALL, while maintaining the significant survival benefits that have been achieved during the past 20 years.