AML

Mutant Isocitrate Dehydrogenase 1 Inhibitor Ivosidenib in Combination with Azacitidine for Newly Diagnosed Acute Myeloid Leukemia

In the January 1, 2021 edition of Journal of Clinical Oncology, Courtney DiNardo and colleagues reported on the combination trial of the IDH1 inhibitor, ivosidenib plus azacitidine, for newly diagnosed AML in the study: Mutant Isocitrate Dehydrogenase 1 Inhibitor Ivosidenib in Combination with Azacitidine for Newly Diagnosed Acute Myeloid Leukemia in the December 20, 2020 edition of Journal of Clinical Oncology. The trial was initiated after preclinical work suggested that addition of azacitidine to ivosidenib enhances mIDH1 inhibition–related differentiation and apoptosis. The trial was an open-label, multicenter, phase Ib trial with dose-finding and expansion stages evaluating safety and efficacy of combining ivosidenib 500 mg once daily with subcutaneous azacitidine 75 mg/m2 on days 1-7 in 28-day cycles in newly diagnosed mutant IDH1 AML patients who were not eligible for intensive induction chemotherapy. 23 patients received ivosidenib plus azacitidine (median age, 76 years; range, 61-88 years). Treatment-related grade ≥ 3 adverse events occurring in > 10% of patients including neutropenia (22%), anemia (13%), thrombocytopenia (13%), and QT prolongation (13%). Important adverse events were all-grade IDH differentiation syndrome (17%), all-grade electrocardiogram QT prolongation (26%), and grade 3 or higher leukocytosis (9%). The median duration or treatment was 15.1 months (range, 0.3-32.2 months). The ORR was 78.3% (18/23 patients; 95% CI, 56.3% to 92.5%), and the CR rate was 60.9% (14/23 patients; 95% CI, 38.5% to 80.3%). After a median follow-up of 16m, the median duration of response in responders had not been reached. The 1 year survival estimate was 82.0% (95% CI, 58.8% to 92.8%). mIDH1 clearance in bone marrow using BEAMing was seen in 71.4% of patients achieving complete remission.

The authors concluded “ Ivosidenib plus azacitidine was well tolerated, with an expected safety profile consistent with monotherapy with each agent. Responses were deep and durable, with most complete responders achieving mIDH1 mutation clearance.”

Reference:

Mutant Isocitrate Dehydrogenase 1 Inhibitor Ivosidenib in Combination with Azacitidine for Newly Diagnosed Acute Myeloid Leukemia

Mutant Isocitrate Dehydrogenase 1 Inhibitor Ivosidenib in Combination With Azacitidine for Newly Diagnosed Acute Myeloid Leukemia | Journal of Clinical Oncology (ascopubs.org)

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