The FDA approved ivosidenib (Tibsovo, Servier Pharmaceuticals) for adult patients with relapsed or refractory myelodysplastic syndromes (MDS) with a susceptible isocitrate dehydrogenase-1 (IDH1) mutation, as detected by an FDA-approved test.

The FDA also approved the Abbott RealTime IDH1 Assay as a companion diagnostic device to select patients for ivosidenib.

Approval was based on trial AG120-C-001, an open-label, single-arm, multicenter trial of 18 adult patients with relapsed or refractory MDS with an IDH1 mutation. IDH1 mutations were detected in peripheral blood or bone marrow by a local or central diagnostic test and confirmed retrospectively by the Abbott RealTime IDH1 Assay.

Ivosidenib was administered orally at a starting dose of 500 mg daily continuous for 28-day cycles until disease progression, unacceptable toxicity or hematopoietic stem cell transplantation. The median treatment duration was 9.3 months. One patient underwent a stem cell transplant following ivosidenib.

Efficacy was established by the rate of complete remission (CR) or partial remission (PR) (2006 International Working Group response for MDS), CR+PR durations, and conversion rate from transfusion dependence to independence. All observed responses were CRs. The CR rate was 38.9% (95% CI, 17.3%-64.3%). The median time to CR was 1.9 months (range, 1.0-5.6 months) and the median CR duration was not estimable (range, 1.9 to 80.8+ months). Among nine patients dependent on red blood cell (RBC) and/or platelet transfusions at baseline, six (67%) became independent of RBC and platelet transfusions during any 56-day post-baseline period. Of the nine patients independent of both RBC and platelet transfusions at baseline, seven (78%) remained transfusion independent during any 56-day post-baseline period.

The most common adverse reactions were similar to common adverse reactions observed with ivosidenib monotherapy for acute myeloid leukemia. These include gastrointestinal toxicities (diarrhea, constipation, mucositis and nausea), arthralgia, fatigue, cough, myalgia and rash. Ivosidenib also may cause QTc prolongation.

The prescribing information contains a boxed warning alerting healthcare professionals and patients about the risk for differentiation syndrome, which may be life-threatening or fatal.

View the full prescribing information for Tibsovo.

—Clinical Oncology News Staff

Based on a press release from the FDA.