An experimental drug for patients with acute myeloid leukemia (AML) with mutations in the gene encoding isocitrate dehydrogenase 1 (IDH1) was found to be safe with durable remissions.
Patients with relapsed or refractory acute myeloid leukemia (AML) with mutations in the gene encoding isocitrate dehydrogenase 1 (IDH1) who were treated with 500 mg of ivosidenib daily had durable remissions. Approximately 6% to 10% of patients with AML have IDH1 mutations.
The experimental drug, which inhibits IDH1, was also found to be safe, with a low frequency of grade 3 or higher treatment-related adverse events. The findings were published in New England Journal of Medicine and presented at the American Society of Clinical Oncology Annual Meeting, held June 1-5.
Ivosidenib is an oral, targeted, small-molecule inhibitor of mutant IDH1. A similar drug targeting IDH2—which occurs in approximately 9% to 13% of patients with AML—is already approved in the United States. The study on ivosidenib assessed a number of outcomes, including safety, maximum tolerated dose, and clinical activity of the drug in patients.
A total of 258 patients were administered a daily dose of ivosidenib as part of the phase I, multicenter, open-label, dose-escalation (78 patients) and dose-expansion (180 patients) study. There were 125 patients in the primary efficacy population. They received 500 mg of ivosidenib daily with at least 6 months of follow-up. The primary efficacy end point was the rate of complete remission or complete remission with partial hematologic recovery.
In the primary efficacy group, the rate of complete remission or complete remission with partial hematologic recovery was 30.4%, with a median duration of 8.2 months. The overall response rate was 41.6%. The results are encouraging, the authors wrote.
“Currently available nontargeted therapies for an unselected population of patients with relapsed or refractory AML were associated with a rate of complete remission of 15% or less and a median overall survival of less than 4 months, with 30-day mortality of approximately 15% and 60-day mortality of approximately 30%,” they explained.
The most common treatment-related adverse events of grade 3 or higher were prolongation of the QT interval (7.8%), IDH differentiation syndrome (3.9%), anemia (2.2%), thrombocytopenia or a decrease in platelet count (3.4%), and leukocytosis (1.7%).
DiNardo CD, Stein EM, de Botton S, et al. Durable remissions with ivosidenib in IDH1-mutated relapsed or refractory AML [published online June 2, 2018]. N Engl J Med. doi: 10.1056/NEJMoa1716984.