What Are the Advantages of Immunotherapy-Based Backbones in Ph+ B-ALL?

Patients with Philadelphia (Ph)-positive B-cell acute lymphoblastic leukemia (B-ALL) may experience an improvement in quality-of-life (QOL) with an immunotherapy-based backbone vs a chemotherapy-based backbone, according to Hannah Goulart, MD.

Goulart, a hematology oncology fellow at the MD Anderson Cancer Center, discussed findings from a poster she presented at the 2025 American Society of Hematology (ASH) Annual Meeting and Exposition, titled “Blinatumomab and ponatinib demonstrates ongoing efficacy as frontline therapy in Philadelphia positive B-cell acute lymphoblastic leukemia: Long-term follow-up from a phase II study”. Therein, her team found that the combination of blinatumomab (Blincyto) and ponatinib (Iclusig), a pan-BCR-ABL tyrosine kinase inhibitor, displayed ongoing efficacy among patients with Ph-positive B-ALL.

She initially discussed considerations when treating these patients with central nervous system (CNS)-disease–directed strategies, particularly among patients with an elevated risk of CNS relapse. Then, she followed up by identifying the primary QOL advantage with the blinatumomab-based regimen, which correlates with a reduction of chemotherapy-related adverse effects.

Transcript:

How might CNS-disease–directed strategies impact therapeutic strategies surrounding this blinatumomab combination?

If this combination is adapted into the community, and as we are shifting away from more intensive chemotherapy backbones to these immunotherapy-based backbones, the focus needs to be on minimizing the risk of CNS relapse. [Also], making sure that we are identifying patients at baseline who have an increased risk of CNS relapse, such as those with elevated white blood cell counts, so that we can mitigate the [relapse risk] using these strategies, such as incorporating 2 cycles of intensive chemotherapy into this regimen and increasing the number of intrathecal chemotherapies.

With 3 years of follow-up, how might the use of this blinatumomab combination impact patient QOL compared with other standards of care?

With the elimination of intensive chemotherapy, now patients who are receiving an immunotherapy-based regimen are not experiencing the long-term [adverse] effects that may be associated with intensive chemotherapy. They are receiving immunotherapy for a definite period of time. They remain on ponatinib long term.

Eliminating intensive chemotherapy for these patients has [positive] impacts on QOL long-term, because we are avoiding these toxicities that could be associated with [this modality] for many patients.

Reference

Goulart H, Jabbour E, Jain N, et al. Blinatumomab and ponatinib demonstrates ongoing efficacy as frontline therapy in Philadelphia positive B-cell acute lymphoblastic leukemia: long-term follow-up from a phase 2 study. Blood. 2025;146(suppl 1):1571. doi:10.1182/blood-2025-1571