Dr DiNardo on the FDA Approval of Ivosidenib in Relapsed/Refractory, IDH1+ MDS

Courtney D. DiNardo, MD, MSCE, associate professor, Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, associate member, The University of Texas Graduate School of Biomedical Sciences at Houston, discusses the significance of the FDA approval of ivosidenib (Tibsovo) in patients with relapsed/refractory, IDH1-mutated myelodysplastic syndromes (MDS).

On October 24, 2023, the FDA granted approval to ivosidenib for the treatment of adult patients with relapsed/refractory MDS harboring a suspected IDH1 mutation. This regulatory decision was supported by findings from the phase 1 AG120-C-001 trial (NCT02074839), which investigated the agent in 18 patients with relapsed/refractory, IDH1-positive MDS. All responders achieved a complete response (CR), and the CR rate was 38.9% (95% CI, 17.3%-64.3%). Additionally, the median time to CR was 1.9 months (range, 1.0-5.6), and the median duration of CR was not evaluable (range, 1.9 months-80.8+ months).

Furthermore, of the 9 patients dependent on red blood cell (RBC) and/or platelet transfusions at baseline, 67% became RBC and transfusion independent during any 56-day post-baseline time frame. In addition, of the 9 patients who were RBC and platelet transfusion–independent at baseline, 78% maintained transfusion independence during any 56-day post-baseline time frame.

Regarding safety, the most common adverse effects seen with ivosidenib in the pivotal trial included gastrointestinal toxicities, fatigue, arthralgia, cough, rash, and myalgia.

This approval is exciting because ivosidenib is a well-tolerated, oral, targeted therapy for the subset of patients with MDS who have IDH1-positive disease, DiNardo says. This approval is for patients whose disease has progressed on standard-of-care therapies, such as hypomethylating agents, DiNardo explains, for which no approved therapies existed prior to this approval. Although patients with relapsed/refractory, IDH1-positive MDS comprise a small subset of patients with MDS, this approval is important and highlights the existence of an effective treatment option for this population, DiNardo concludes.