Dr Jabbour on Frontline Treatment Considerations in ALL

"Every patient should have a full profile from the biology point of view. [If I have a patient who is] Philadelphia chromosome [Ph]–positive, they have a specific treatment. Then I move to [determine if patients in the] frontline [have] Ph-negative B-cell, T-cell, Burkitt lymphoma, or Ph-like ALL…and then all other patients."

Elias Jabbour, MD, professor, Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses important frontline treatment considerations in newly diagnosed acute lymphocytic leukemia (ALL).

Treatment decisions for ALL are influenced by several critical factors, including patient age, immune phenotype, and disease biology, Jabbour begins. These factors guide initial therapy and help determine subsequent strategies such as transplantation or CAR T-cell therapy.

Patient age is a key consideration, as younger individuals generally tolerate intensive therapies better than older patients, Jabbour states. Older adults often have comorbidities and reduced tolerance to aggressive chemotherapy, necessitating tailored approaches to improve outcomes and minimize toxicity.

The immune phenotype, specifically whether the disease is B-cell or T-cell ALL, also dictates treatment strategies, he continues. Philadelphia chromosome (Ph)–positive ALL, for instance, requires TKIs such as imatinib (Gleevec) or dasatinib (Sprycel) combined with either chemotherapy or immunotherapy, Jabbour details. Conversely, patients with Ph-like or Ph-negative ALL follow distinct treatment pathways, emphasizing the need for comprehensive diagnostic profiling, he says.

Biological characteristics of the leukemia, such as hypodiploidy or other high-risk features, play a crucial role in planning post-remission therapy, Jabbour notes. For example, patients with hypodiploidy or other aggressive markers may benefit from frontline immunotherapy trials, yet they are likely candidates for subsequent transplantation to achieve durable remission, he explains. Similarly, patients with Burkitt's lymphoma or double-negative lineage ALL require unique therapeutic approaches, Jabbour adds.

Although up-front induction therapy may not always be heavily influenced by specific biological markers, these factors are critical for long-term treatment decisions, such as whether to pursue transplant as consolidation, Jabbour concludes.