Targeted Therapy With Ivosidenib Improves Hematologic Recovery in Mutant-IDH1 Relapsed or Refractory MDS

Praneeth Baratam, MBBS, Medical University of South Carolina/Hollings Cancer Center, Charleston, presented new data from a phase 1 substudy revealing that ivosidenib, a mutant isocitrate dehydrogenase 1 (IDH1) inhibitor, achieves rapid and sustained hematologic improvement in patients with relapsed or refractory myelodysplastic syndrome (MDS) harboring IDH1 mutations.¹ These findings provide evidence of ivosidenib’s potential to address unmet needs in a rare, high-risk population.

Somatic IDH1 mutations are present in approximately 3% of patients with MDS and are associated with poor prognosis and an increased risk of progression to acute myeloid leukemia.^2,3 Ivosidenib, a targeted oral therapy inhibiting mutant IHD1, is approved to treat patients with mutant IDH1 relapsed or refractory MDS. This new analysis evaluated the impact of ivosidenib on hematologic recovery, transfusion independence, and blood count kinetics.

The phase 1 trial enrolled 18 patients with mutant IDH1 relapsed or refractory MDS. Participants received oral ivosidenib at 500 mg daily in 28-day cycles with a median treatment duration of 9.3 months. Absolute neutrophil counts increased significantly from a baseline mean of 0.8 × 10⁹/L to 3.7 × 10⁹/L by day 15 of cycle 1, remaining stable above 2.0 × 10⁹/L for the majority of treatment duration. Even among patients who did not achieve complete remission (CR), 36.4% showed neutrophil improvement, and 18.2% and 18.2% demonstrated erythroid and platelet improvements, respectively. Most patients achieving marrow CR also attained transfusion independence, with 87.5% gaining platelet independence and 75% achieving red blood cell independence.

These study findings demonstrate that ivosidenib treatment leads to rapid and sustained hematologic response in patients with mutant IDH1 relapsed or refractory MDS, independent of treatment response status. In addition, most patients who did not achieve CR also experienced sustained hematologic improvement and transfusion independence. Dr. Baratam concluded, “These additional data augment the clinical benefit of ivosidenib in patients with mutant-IDH1 MDS and support the ongoing development in a phase 3 study of ivosidenib in first-line MDS.”

References

1. Prince GT, Baratam P, Garcia-Manero G, et al. Improved hematologic recovery with ivosidenib in patients with mIDH1 relapsed or refractory MDS: results from a phase 1 substudy. Abstract #3226. Presented at the American Society of Hematology Annual Meeting; December 7-10, 2024; San Diego, California.
2. Patnaik MM, Hanson CA, Hodnefield JM, et al. 2012;26:101-105. doi: 10.1038/leu.2011.298
3. DiNardo CD, Jabbour E, Ravandi F, et al. Leukemia. 2016;30:980-984. doi: 1038/leu.2015.211