Ivosidenib gives encouraging results in IDH1-mutated high-risk AML
medwireNews: Ivosidenib induces durable remission in nearly a third of patients with isocitrate dehydrogenase 1 (IDH1)-mutated relapsed or refractory acute myeloid leukemia (AML), phase 1 study data show.
The study, by Courtney DiNardo (University of Texas M.D. Anderson Cancer Center, Houston, USA) and colleagues, also found that the oral, targeted, small-molecule inhibitor of the mutated IDH1 protein was associated with a low rate of grade 3 or higher treatment-related adverse events when given at a dose of 500 mg daily.
“Additional clinical benefits included the development of transfusion independence and, among patients who had a response, a lower incidence of infections and febrile neutropenia than among those who did not have a response,” the researchers write in The New England Journal of Medicine.
During at least 6 months of follow-up, the most common treatment-related adverse events of grade 3 or higher among the 179 ivosidenib-treated patients in the safety population were prolongation of the QT interval (7.8%), the IDH differentiation syndrome (3.9%), thrombocytopenia or decreased platelet count (3.4%), anemia (2.2%), and leukocytosis (1.7%).
DiNardo and team note that prolongation of the QT interval, the IDH differentiation syndrome, and leukocytosis are ivosidenib-specific adverse events. All of these cases were well managed and none led to permanent discontinuation of treatment.
In the primary efficacy population (n=125), the overall response rate was 41.6%, with 21.6% experiencing complete remission and 30.4% of patients experiencing complete remission or complete remission with partial hematologic recovery (defined as bone marrow myeloblasts <5% combined with both absolute neutrophil count >500/μL and platelet count >50,000/μL).
The median durations of these responses were 6.5, 9.3, and 8.2 months, respectively.
Median overall survival was 8.8 months, but approximately half (50.1%) of patients who had complete remission or complete remission with partial hematologic recovery were still alive at 18 months, compared with less than 10% of patients who did not achieve this outcome.
In addition, patients who experienced complete remission or complete remission with partial hematologic recovery had fewer infections and febrile neutropenia episodes than those who did not have a response.
Among 84 patients who were dependent on red-cell transfusion, platelet transfusion, or both at baseline, 35% achieved transfusion-independence for at least 56 days during treatment.
The investigators also found that seven of 34 patients screened after at least 6 months had no residual detectable IDH1 mutations. All seven of these patients experienced complete remission, which lasted longer than for patients without mutation clearance (median 11.1 vs 6.5 months).
DiNardo and co-authors conclude that “ivosidenib monotherapy […] led to favorable outcomes as compared with historical outcomes in patients with advanced relapsed or refractory AML.”
The study findings were also presented at the ASCO Annual Meeting 2018 in Chicago, Illinois, USA.
By Laura Cowen
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