PURPOSE : IDH1 (isocitrate dehydrogenase 1) mutations occur in 5-10% of patients with acute myeloid leukemia (AML). Ivosidenib is an IDH1 inhibitor, approved for use in patients with IDH1-mutated AML.

PATIENTS AND METHODS : We conducted a multi-center, phase I trial of maintenance ivosidenib following allogeneic hematopoietic cell transplantation (HCT) in patients with IDH1-mutated AML. Ivosidenib was initiated between days 30 and 90 following HCT and continued for up to twelve 28-day cycles. The first dose level was 500mg daily, with level reduction to 250mg daily, if needed, in a 3x3 de-escalation design. Ten additional patients would then receive the maximum tolerated (MTD) or recommended phase 2 dose (RP2D). The primary endpoint was establishing the MTD or RP2D of ivosidenib.

RESULTS : Eighteen patients were enrolled, of whom 16 initiated post-HCT ivosidenib. One dose limiting toxicity, grade(g) 3 QTc prolongation, was observed. The RP2D was established at 500mg daily. Attributable g≥3 adverse events were uncommon, with the most common being QTc prolongation in 2 patients. Eight patients discontinued maintenance, with only one due to adverse event. Six-month cumulative incidence (CI) of gII-IV aGVHD was 6.3%, and two-year CI of all cGVHD was 63%. Two-year CI of relapse and non-relapse mortality (NRM) were 19% and 0%, respectively. Two-year progression-free (PFS) was 81%, and two-year overall survival (OS) was 88%.

CONCLUSIONS : Ivosidenib is safe and well-tolerated as maintenance therapy following HCT. Cumulative incidence of relapse and NRM, as well as estimations of PFS and OS, were promising in this phase 1 study.