SOHO State of the Art Updates and Next Questions | SOHO 2025 Next Questions: Acute Lymphoblastic Leukemia

The treatment landscape of B-cell acute lymphoblastic leukemia (B-ALL) has been transformed by the incorporation of immunotherapy and potent tyrosine kinase inhibitors (TKIs) into frontline regimens, resulting in meaningful improvements in long-term survival. Such advances have allowed for a reduction in both the intensity and duration of chemotherapy without compromising outcomes, a particularly important goal for older adults, who are less tolerant to intensive chemotherapy and often harbor higher-risk disease features, including TP53 mutations that confer resistance to traditional chemotherapy. Largely chemotherapy-free regimens may alleviate some of the poor outcomes that older patients experience; such regimens are under investigation. While the risk factors that portend inferior outcomes for patients with Philadelphia (Ph)-positive B-ALL are still being defined in the setting of immunotherapy-based regimens and more potent TKIs, it is evident that an elevated baseline white blood cell count is a strong predictor of relapse. The role of chimeric antigen receptor (CAR) T-cell therapy as consolidation for patients with high-risk Ph-positive B-ALL is actively being explored, alongside efforts to identify factors that influence CAR T-cell expansion and persistence as determinants of response durability. Advances in more sensitive assessments of measurable residual disease (MRD) using next generation sequencing (NGS) will help inform which patients may benefit from additional consolidative strategies. Novel agents under development include the subcutaneous (SC) form of blinatumomab, which has demonstrated efficacy even in patients with prior blinatumomab exposure. Altogether, these developments frame the next set of questions in ALL, which will be addressed in this review.