| Autor: |
Yi-Bin Chen, Vincent T. Ho, Dylan M. Marchione, Elayne Breton, Jennifer Brock, Jonathan L. Wahl, Lindsey H. Perry, AJ S. Bottoms, Devon Kelley, Laura W. Knight, Alice S. Mims, Philip C. Amrein, Andrew M. Brunner, Steve L. McAfee, Areej El-Jawahri, Zachariah DeFilipp, Annette S. Kim, Shuli Li, Mark J. Levis, Robert J. Soiffer, Haesook T. Kim, Amir T. Fathi |
| Rok vydání: |
2023 |
| DOI: |
10.1158/1078-0432.c.6604888.v1 |
| Popis: |
Purpose:Isocitrate dehydrogenase 1 (IDH1) mutations occur in 5% to 10% of patients with acute myeloid leukemia (AML). Ivosidenib is an IDH1 inhibitor, approved for use in patients with IDH1-mutated AML.Methods:We conducted a multicenter, 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 12 28-day cycles. The first dose level was 500 mg daily, with level reduction to 250 mg daily, if needed, in a 3 × 3 de-escalation design. Ten additional patients would then receive the 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 500 mg 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 2-year CI of all cGVHD was 63%. Two-year CI of relapse and nonrelapse mortality (NRM) were 19% and 0%, respectively. Two-year progression-free (PFS) was 81%, and 2-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 I study. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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