Azacitidine Doublet Demonstrates ‘Encouraging Activity’ in FLT3-Mutated MDS

Azacitidine plus quizartinib achieved a high overall response rate (ORR) and a promising safety profile in patients with myelodysplastic syndromes (MDS) with FLT3 mutations, according to a study published in Leukemia Research.

The phase I trial, led by Guillermo Montalban-Bravo, MD, of the University of Texas MD Anderson Cancer Center, included 12 patients with hypomethylating agent-naïve MDS or MDS/myeloproliferative neoplasms (MPN). Following a 3+3 design, the study evaluated three dose levels of quizartinib (30 mg, 40 mg, and 60 mg) in combination with azacitidine. The maximum tolerated dose was not reached.

The combination achieved an ORR of 83%, a median relapse-free survival of 15.1 months (95% CI, 0.0-38.4 months), and an overall survival of 7.5 months (95% CI, not calculable). Four (57%) patients achieved FLT3 mutation clearance.

As for safety, the most common grade 3 and 4 treatment-related adverse events included thrombocytopenia (n=5; 42%), anemia (n=4; 33%), lung infection (n=2; 17%), skin infection (n=2; 17%), hyponatremia (n=2; 17%), and sepsis (n=2; 17%).

“These data suggest quizartinib is safe and shows encouraging activity in FLT3-mutated MDS and MDS/MPN,” Dr. Montalban-Bravo and colleagues concluded.

Reference

Montalban-Bravo G, Jabbour E, Chien K, et al. Phase 1 study of azacitidine in combination with quizartinib in patients with FLT3 or CBL mutated MDS and MDS/MPN. 2024. Leuk Res. 2024. doi:10.1016/j.leukres.2024.107518