What Now Predicts Outcomes in Older Adults With ALL: Emily K. Curran, MD

The prognostic landscape for older adults with acute lymphoblastic leukemia (ALL) has shifted dramatically in recent years, according to Emily K. Curran, MD, associate professor of internal medicine at the University of Cincinnati College of Medicine.

In a recent interview with The American Journal of Managed Care^®, she explained that Philadelphia chromosome–positive ALL, which follows a bimodal distribution and is common in both young children and older adults, was historically considered a poor prognostic marker; patients who achieved remission frequently relapsed, and outcomes were grim. That has changed substantially with the incorporation of tyrosine kinase inhibitors, which specifically target the Philadelphia chromosome, along with newer immunotherapy approaches.

“We now say that that’s no longer a poor prognostic,” Curran noted, reflecting on the rapid evolution since her time in medical school. Many disease biologies once considered harbingers of poor outcomes are being reevaluated as novel treatments emerge for ALL. Still, challenges remain.

T-cell ALL presents a particular hurdle, not necessarily because patients fare worse biologically but because the therapeutic arsenal is thinner. Much of the immunotherapy innovation in ALL has been directed at markers on B cells in B-cell ALL, leaving T-cell ALL with fewer novel treatment options—a gap that becomes especially consequential in older adults who cannot tolerate intensive chemotherapy regimens.

KMT2A rearrangement, formerly known as mixed lineage leukemia, remains a genuinely difficult disease biology. This chromosomal alteration, which can occur in both acute myeloid leukemia (AML) and ALL, is still associated with lower rates of remission and higher rates of relapse. However, Curran expressed optimism about menin inhibitors, which are now being used in both AML and ALL.

Her hope is that KMT2A-rearranged leukemias will follow the same trajectory as Philadelphia chromosome–positive ALL: a marker that carries a poor prognosis today but may not in the near future as targeted treatments continue to advance.