Dr DeAngelo on Key Questions to Address in Acute Lymphoblastic Leukemia Management

Daniel J. DeAngelo, MD, PhD, physician and chief of the Division of Leukemia at Dana-Farber Cancer Institute and professor of medicine at Harvard Medical School, discussed the evolving treatment strategies in acute lymphoblastic leukemia (ALL) management, particularly for patients with Philadelphia chromosome (Ph)–positive disease, which were discussed during the 2026 Bridging the Gaps in Leukemia, Lymphoma, and Multiple Myeloma Conference.

DeAngelo began by highlighting that major academic centers have shifted toward chemotherapy-light or chemotherapy-free induction regimens in recent years for patients with Ph-positive ALL. He noted that this frontline strategy typically consists of a TKI combined with corticosteroids, often followed by the bispecific T-cell engager blinatumomab (Blincyto), which historically has served as a bridge to allogeneic stem cell transplant.

However, emerging data from The University of Texas MD Anderson Cancer Center suggest that some patients may be able to avoid transplant altogether if they have undetectable BCR-ABL1 transcripts and undetectable minimal residual disease at a 10^-6 sensitivity per clonoSEQ, DeAngelo asserted.

He also highlighted data from the phase 3 GIMEMA ALL2820 trial (NCT04722848), which were presented at the 2025 ASH Annual Meeting and Exposition. Initial results demonstrated that patients with Ph-positive ALL achieved superior outcomes with a chemotherapy-free induction strategy of ponatinib (Iclusig) plus blinatumomab vs imatinib (Gleevec) plus chemotherapy. According to DeAngelo, these findings further reinforce the ongoing shift toward less intensive yet highly effective induction treatment approaches.

Despite this progress, several important questions remain, DeAngelo said. One key uncertainty involves optimal TKI selection, particularly for older patients or those with significant cardiovascular comorbidities. DeAngelo noted that clinicians must weigh whether to use ponatinib or alternative TKIs in individuals with elevated cardiovascular risk.

Additional unresolved issues include identifying the most clinically meaningful high-risk features, such as elevated white blood cell counts, that could influence treatment decisions, along with developing strategies to mitigate central nervous system relapse. Determining which patients still derive clear benefit from transplant and establishing the optimal duration of TKI therapy also remain areas of active investigation, he said.