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Potential of IDH1 Inhibitors in AML Prior to Hematopoietic Cell Transplantation

By: Julia Fiederlein
Posted: Friday, October 16, 2020

Courtney D. DiNardo, MD, MSCE, of The University of Texas MD Anderson Cancer Center, Houston, and colleagues conducted a multicenter study to assess hematopoietic cell transplantation (HCT) outcomes in patients with isocitrate dehydrogenase 1 (IDH1)-mutated relapsed or refractory acute myeloid leukemia (AML) who responded to ivosidenib monotherapy. This IDH1 inhibitor has been approved in the United States as a first-line treatment of AML with this mutation. The results of this early-phase trial were presented during the virtual edition of the 2020 Society of Hematologic Oncology (SOHO) Annual Meeting (Abstract AML-262).

“Mutations in IDH1 result in the production of D-2-hydroxyglutarate,” the investigators commented. “D-2-hydroxyglutarate production is suppressed through targeted inhibition of the mutant IDH1 enzyme, which restores cell differentiation.”

A total of 179 patients received 500 mg of daily ivosidenib. During dose escalation, the experimental treatment was administered in doses ranging from 200 to 1,200 mg daily. According to the investigators, 18 patients who achieved an adequate response were eligible for HCT after discontinuation of ivosidenib.

Prior to HCT, 66.7% of patients achieved complete remission. The median overall survival was higher in the HCT subgroup than in the overall study cohort (16.8 vs. 9.0 months, respectively). In the HCT subgroup, the 6- and 12-month overall survival rates were 94.4% and 61.1%, respectively. For patients achieving complete remission, the median overall survival was not estimable in the HCT subgroup and was 20.5 months in those who did not undergo HCT.

After HCT, the median relapse-free survival was 7.3 months; the 6- and 12-month relapse-free survival rates were 58.8% and 47.1%, respectively. The overall survival rate was 77.8% at 6 months and 50.0% at 12 months. In the HCT subgroup, the investigators reported the clearance of mutated IDH1 in 8.3% of patients with a best overall response of complete remission.

Disclosure: No information regarding conflicts of interest was provided.



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