Dr DeAngelo on the Importance of Consensus Guidelines for Treating Acute Lymphoblastic Leukemia

Daniel DeAngelo, MD, PhD, chief, Division of Leukemia, Dana-Farber Cancer Institute, and professor of medicine, Harvard Medical School, highlights the challenges of treating acute lymphoblastic leukemia (ALL), a rare malignancy that accounts for a small proportion of leukemia cases. Given the disease’s relative infrequency outside of large academic centers, standardizing diagnostic and therapeutic approaches is essential for ensuring consistent care. These considerations were discussed at the Bridging The Gaps: Leukemia, Lymphoma, and Multiple Myeloma meeting in Miami, Florida.

Given the rarity of ALL, which accounts for approximately 1% to 2% of all malignancies and 10% to 15% of acute leukemias, treatment strategies must balance efficacy with toxicity considerations, particularly in older and high-risk patient populations, Deangelo says.

ALL treatment has historically relied on intensive, multi-agent chemotherapy regimens, with pediatric-inspired protocols increasingly adopted for younger patients. However, DeAngelo highlights that these regimens may not be suitable for older patients, particularly those over 55 or 60 years of age, due to higher toxicity risks and treatment-related morbidity. Defining "older" in this context remains unclear, necessitating a more individualized approach. A reduced-intensity regimen incorporating novel targeted agents such as blinatumomab (Blincyto) or inotuzumab ozogamicin (Besponsa) may provide a more tolerable alternative for older adults without affecting therapeutic efficacy.

Another challenge in standardizing treatment is the heterogeneity between Philadelphia chromosome (Ph)–positive and Ph-negative ALL, Deangelo continues. TKIs combined with chemotherapy have transformed the treatment landscape for Ph-positive disease, but the optimal sequencing and combination of TKIs with other therapies remain an area of ongoing investigation. In Ph-negative ALL, incorporating monoclonal antibodies and targeted agents into chemotherapy backbones has improved outcomes, but no clear consensus exists on the most effective regimen.

DeAngelo underscores the necessity of expert-driven treatment guidelines to bridge the gap between clinical trial findings and real-world practice, particularly in community oncology settings where ALL is less frequently encountered. Standardized protocols help define optimal induction regimens, guide decisions regarding minimal residual disease monitoring, and refine indications for allogeneic hematopoietic stem cell transplantation.

Prospective studies remain necessary to clarify key aspects of ALL management, including the role of reduced-intensity chemotherapy in older patients, the optimal integration of novel immunotherapies, and the use of measurable residual disease as a treatment-guiding biomarker. Establishing a treatment consensus through expert collaboration is essential to optimizing outcomes and ensuring that advances in ALL therapies are effectively implemented across diverse clinical settings.