Oral Monotherapy Produces Significant Response in IDH1-Mutated MDS

Oral ivosidenib monotherapy shows promise in mutant IDH1 myelodysplastic syndromes (MDS), according to final results data from the phase II IDIOME trial. Researchers reported the data at the European Hematology Association 2024 Hybrid Congress in Madrid, Spain.

“Ivosidenib monotherapy was associated with significant responses in all mutant IDH1 MDS patient cohorts and, in this frail population, was well tolerated,” the trial investigators summarized.

The total IDIOME study cohort included 48 patients, was 50% female, and had a median age of 76.5 years. Patients were divided into three cohorts, and patients in all cohorts received continuous 28-day cycles of ivosidenib 500 mg once daily.

The first cohort comprised 22 patients with high-risk disease in whom prior azacitidine therapy had been unsuccessful. An overall hematological response after three cycles was achieved in 63.6% of these patients, and the median duration of response was 4.8 months. The median overall survival (OS) was 8.9 months, and the 12.0-month OS rate was 15.2%.

The second cohort included 23 patients with high-risk disease receiving ivosidenib as first-line treatment. If these patients had no response after three cycles of ivosidenib, they were administered azacitidine. An overall hematological response after three cycles was achieved in 78.3%, and the 12-month OS rate was 91.3%. Azacitidine was added in three patients and did not produce an additional response.

“The high overall hematological response rate and prolonged [OS] observed in treatment-naive high-risk MDS patients suggest that ivosidenib monotherapy could be a first-line treatment in this population, including in candidates for hematopoietic stem cell transplantation,” the investigators added regarding results from the second cohort.

The third cohort comprised three patients with low-risk disease and in whom prior erythropoietin therapy had been unsuccessful. Two patients achieved complete response and had no disease progression as of the study’s conclusion. The third patient died two years after study inclusion following 13 cycles of treatment.

Regarding safety findings, 21 treatment-related adverse events were reported by nine patients. Most of these events were differentiation syndrome, and all were reversible.

Reference

Sébert M, Clappier E, Cluzeau T, et al. Ivosidenib monotherapy in IDH1 mutated myelodysplastic syndrome, final results of the IDIOME trial, a GFM study. Abstract #S182. Presented at the European Hematology Association 2024 Hybrid Congress; June 13-16, 2024; Madrid, Spain.