New Standards in Ph+ and High-Risk ALL

Naval G. Daver, MD, professor, Department of Leukemia, Division of Cancer Medicine, and director, Department of Leukemia, Division of Leukemia Research Alliance Program, The University of Texas MD Anderson Cancer Center, summarizes recent advances in the management of acute lymphoblastic leukemia (ALL), with a focus on immunotherapy and targeted agents. The session featured contributions from several experts from MD Anderson Cancer Center.

One of the key topics was the use of blinatumomab in combination with tyrosine kinase inhibitors (TKIs) for frontline treatment of Philadelphia chromosome–positive ALL. Data show high remission rates, measurable residual disease (MRD) clearance, and long-term survival exceeding 90% in both younger and older patients, suggesting this regimen may be emerging as a new standard of care.

The role of blinatumomab as an MRD-directed therapy or as maintenance after intensive chemotherapy was also discussed. Findings from the ECOG-ACRIN E1910 trial indicate that incorporating blinatumomab after frontline chemotherapy improves survival in patients who are MRD-negative by flow cytometry, establishing this approach as a new standard in certain settings.

Another major topic was the evolving role of chimeric antigen receptor (CAR) T-cell therapy in ALL. While currently approved in the relapsed/refractory setting, emerging evidence suggests CAR T-cell therapy may be effective as consolidation or maintenance for high-risk or MRD-positive patients, potentially reducing the need for allogeneic stem cell transplantation. Newer CAR T-cell constructs, such as obe-cel, are showing promising tolerability, efficacy, and durability.

Dr. Daver highlights that the past decade has seen a shift away from traditional chemotherapy toward targeted TKIs, antibody-based immunotherapies (blinatumomab, inotuzumab), and cellular therapies, resulting in significantly improved survival for patients across age groups.