Fathi AT, Kim HT, Soiffer RJ, et al. Multi-Center Phase I Trial of Ivosidenib as Maintenance Treatment Following Allogeneic Hematopoietic Cell Transplantation for IDH1-Mutated Acute Myeloid Leukemia. Clinical Cancer Research. 2023; (doi: 10.1158/1078-0432.CCR-23-0182).
A Phase I trial testing the isocitrate dehydrogenase 1 (IDH1) inhibitor ivosidenib as maintenance therapy in patients with IDH1-mutated acute myeloid leukemia following allogeneic hematopoietic cell transplantation (HCT) found that it was safe and well-tolerated. For the study, patients with IDH1-mutated AML initiated ivosidenib between days 30 and 90 after HCT and continued for as many as 12 28-day cycles. A 500-mg daily dose was initially administered, then reduced to 250-mg daily, if needed. The maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) was then given to 10 additional patients. Sixteen of 18 enrolled patients initiated post-HCT ivosidenib. The data show there was one dose limiting toxicity, grade 3 QTc prolongation. The RP2D was set at a daily dose of ivosidenib 500 mg. QTc prolongation was observed in two patients. Eight patients halted maintenance; however, only one case was the result of an adverse event. The 6-month cumulative incidence (CI) of grade II-IV acute graft-versus-host-disease (GVHD) and 2-year CI of chronic GVHD were 6.3% and 63%, respectively. At 2 years, the respective CIs of relapse and non-relapse mortality were 19% and 0%, while progression-free survival and overall survival were 81% and 88%, respectively.
Tags: GVHD, Relapse, acute, Transplant, Acute GVHD, graft, nonrelapse, graft-vs-host disease, graft-versus-host, acute myeloid leukemia