Treatment of Older Adults with Newly Diagnosed Philadelphia Chromosome-Negative Acute Lymphoblastic Leukemia

Approximately half of newly diagnosed cases of acute lymphoblastic leukemia (ALL) occur in adults, but adults experience significantly higher rates of treatment failure and treatment-related mortality due to frequent presence of adverse disease biology and limited tolerability of conventional chemotherapy.

Here, we discuss recent data from clinical trials investigating new approaches for initial treatment of Philadelphia chromosome-negative ALL in older adults. These trials investigate the incorporation of novel agents including the anti-CD22 antibody-drug conjugate inotuzumab, the CD19-CD3 bi-specific T-cell engager blinatumomab, and the BCL2 inhibitor venetoclax into treatment regimens, with some studies attenuating or omitting chemotherapy. We also discuss the role of allogeneic stem cell transplantation consolidation for this population and highlight the possibility of frontline CD19-directed chimeric antigen receptor T-cell therapy consolidation approaches for B-ALL. Finally, we discuss improved understanding of the genetic diversity of ALL in older adults including occurrence of ALL with TP53 mutation, ALL with myeloid gene mutations, and therapy-related ALL.

Overall, we highlight progress for older adults with Ph-negative ALL with patients more frequently achieving a measurable residual disease-negative complete remission, but significant work remains to improve the safety of treatment as well as the depth and durability of treatment response.