FDA Approval of Revumenib for R/R, NPM1-Mutant AML: Eytan M. Stein, MD
Eytan M. Stein, MD, of Memorial Sloan Kettering Cancer Center, discussed the FDA approval of revumenib (Revuforj) for use in adult and pediatric patients with relapsed/refractory acute myeloid leukemia harboring NPM1 mutations, supported by data from the phase 1/2 AUGMENT-101 trial (NCT04065399). He emphasized that revumenib represents the first targeted therapy option for this molecular subtype, which previously lacked mutation-directed options in the relapsed/refractory setting. Stein noted that although NPM1-mutant AML is often curable up front, outcomes after relapse are poor, with median OS historically under 1 year. The oral menin inhibitor offers a generally well-tolerated option that targets the disease biology and expands therapeutic options for this high-risk population.
MRD Responses With Inotuzumab Ozogamicin Plus Dasatinib in Ph+ ALL: Anand Patel, MD
Anand Patel, MD, of the University of Chicago Medicine, shared primary data from a phase 2 study (NCT04747912) examining dasatinib (Sprycel) paired with inotuzumab ozogamicin (Besponsa)–based therapy in patients with newly diagnosed Philadelphia chromosome–positive acute lymphoblastic leukemia. He reported that by the end of the third course of treatment, 100% of patients achieved MR4 or minimal residual disease negativity by next-generation sequencing; 90% achieved MR4. Patel noted that a modified treatment schema eliminated veno-occlusive disease, with no dose-limiting toxicities observed in patients treated with this approach. At a median follow-up of 2.1 years, the 2-year OS rate was 80%, with no central nervous system relapses and no patients requiring allogeneic stem cell transplant.
Second-Line Targeted Therapy in BRAF+ Pediatric Low-Grade Glioma: Mohamed Abdelbaki, MD
Mohamed Abdelbaki, MD, of the University of Washington School of Medicine, discussed evolving second-line treatment approaches for patients with pediatric low-grade glioma (pLGG) and BRAF V600E mutations or BRAF fusions, informed by findings from the phase 2 FIREFLY-1 trial (NCT04775485). He noted that tovorafenib (Ojemda) received accelerated approval from the FDA for use in patients with relapsed or refractory BRAF-positive pLGG based on durable response rates exceeding 50%. Abdelbaki emphasized that treatment selection depends on prior therapies, tolerability, and timing of recurrence. He added that tovorafenib is a favorable option in recurrent disease, particularly for those with BRAF fusions or those who have not had prior exposure to dabrafenib (Tafinlar) and trametinib (Mekinist).
Bezuclastinib in Non-Advanced Systemic Mastocytosis from the SUMMIT Trial: Tracy I. George, MD
Tracy George, MD, of ARUP Laboratories and the University of Utah, discussed pathobiologic data from the phase 2 SUMMIT trial (NCT05186753) examining bezuclastinib (CGT9486) in patients with nonadvanced systemic mastocytosis. She reported marked normalization of bone marrow features, including reductions in mast cell aggregates, spindle-shaped mast cells, and KIT D816V variant allele frequency vs placebo. Moreover, 97% of patients who received bezuclastinib achieved at least a 50% reduction in KIT D816V VAF, with many also achieving normalization of serum tryptase levels by week 24. She clarified that more than half of treated patients no longer met World Health Organization diagnostic criteria for nonadvanced systemic mastocytosis at that time point.