Evaluating Ivosidenib in Patients with IDH1-Mutated Myelodysplastic Syndrome

Results from the phase II IDIOME trial suggest that ivosidenib, a small-molecule mutant IDH1 inhibitor, showed good tolerability and significant efficacy in the treatment of three separate cohorts of patients with IDH1-mutated myelodysplastic syndrome (MDS). The findings were presented at the 2021 ASH Annual Meeting.

During her presentation, the study’s lead author Marie Sebert, MD, PhD, noted that “ivosidenib was particularly effective in treatment-naïve, higher-risk MDS patients with IDH1 mutations,” with a response rate of 91%.

The researchers administered continuous 28-day cycles of ivosidenib 500 mg orally once-daily to the following cohorts:

  • patients with higher-risk MDS that previously failed treatment on azacitidine (cohort A, n=29)
  • patients with untreated higher-risk MDS without life-threatening cytopenias (cohort B, n=29)
  • patients with lower-risk MDS that previously failed on erythropoietin (cohort C, n=10)

The primary endpoint was overall response rate (ORR) at three and six months, assessed via complete remission (CR), partial remission (PR), and stable disease with hematologic improvement (HI), as defined by the International Working Group (IWG) 2006. Secondary outcomes included safety, duration of response, event-free survival (EFS), and overall survival (OS). Treatment with azacitidine was added to one non-responding patient in cohort B after three cycles, with no additional response.

At data cutoff, the ORR was 69% with 18 responses including 12 CR, one PR, and five HI. Seventeen of the 18 patients achieved their response after three cycles. The median response duration was 7.4 months. In the whole cohort, the median OS was 14 months. Twelve patients had disease progression and 11 patients died, mostly due to relapse or progression.

Five serious treatment-related adverse events were reported, four of which were differentiation syndrome. One patient had febrile neutropenia related to ivosidenib treatment that was resolved without issue.

Though the preliminary results were encouraging, Dr. Sebert acknowledged that their findings need to be confirmed in larger patient populations. The article noted that the IDIOME study is ongoing, and molecular monitoring results of IDH1 mutations will be published in the future.