Multicenter Phase I Trial of Ivosidenib as Maintenance Treatment Following Allogeneic Hematopoietic Cell Transplantation for IDH1-Mutated Acute Myeloid Leukemia.

Autor:	Fathi AT; Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts., Kim HT; Department of Data Science, Dana-Farber Cancer Institute, Harvard School of Public Health, Boston, Massachusetts., Soiffer RJ; Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts., Levis MJ; Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland., Li S; Department of Data Science, Dana-Farber Cancer Institute, Harvard School of Public Health, Boston, Massachusetts., Kim AS; Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts., DeFilipp Z; Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts., El-Jawahri A; Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts., McAfee SL; Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts., Brunner AM; Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts., Amrein PC; Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts., Mims AS; The Ohio State University Comprehensive Cancer Center, Columbus, Ohio., Knight LW; Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts., Kelley D; Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts., Bottoms AS; Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts., Perry LH; Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts., Wahl JL; Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts., Brock J; Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts., Breton E; Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland., Marchione DM; Servier Pharmaceuticals, Boston, Massachusetts., Ho VT; Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts., Chen YB; Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts.
Jazyk:	angličtina
Zdroj:	Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2023 Jun 01; Vol. 29 (11), pp. 2034-2042.
DOI:	10.1158/1078-0432.CCR-23-0182
Abstrakt:	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. Patients and 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. (©2023 American Association for Cancer Research.)
Databáze:	MEDLINE
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