Ivosidenib Receives Priority Review for the Treatment of Relapsed/Refractory AML

The FDA granted priority review to ivosidenib for the treatment of relapsed/refractory IDH1-mutated AML. The decision was based on results from an ongoing, single-arm, phase I trial that included 258 patients (78 in the dose-escalation phase and 180 in the dose-expansion phase). As of May 12, 2017 (data cutoff), 24 percent of patients (n=62) were continuing treatment, and the median duration of ivosidenib exposure was 3.5 months (range = 0.1-33.5 months). Twenty-two patients (8.5%) discontinued treatment and went on to receive alloHCT.

The most common any-grade AEs (occurring in ≥20% of patients) were diarrhea (33%), leukocytosis (30%), nausea (30%), fatigue (29%), and febrile neutropenia (25%). Twenty-nine participants (11.2%) reported differentiation syndrome (DS), 14 (5.4%) of which were grade ≥3. Treatment was held because of DS in 11 patients (4.3%), but no cases of DS led to permanent treatment discontinuation or death. Disease progression was the most common cause of treatment discontinuation; 12.8 percent stopped treatment because of AEs.

Among 125 patients with relapsed/refractory AML who received ivosidenib 500 mg for a minimum of six months (92 in dose-expansion and 33 in dose-escalation phases), the rate of complete response (CR) or CR with partial hematologic recovery (primary endpoint) was 30.4 percent, which lasted for a median of 8.2 months (95% CI 5.5-12.0; range not provided). The median duration of response was 6.5 months (range not provided). Of those who achieved CR, 28 percent were minimal residual disease–negative.

After 14.8 months of follow-up, the median OS was 8.8 months (range = 6.7-10.2); the median OS was not reached in those who achieved a CR but was 9.3 months for non-responders (range not reported).

Sources: Agios press release, February 15, 2018; DiNardo CD, De Botton S, Stein EM, et al. Ivosidenib (AG-120) in mutant IDH1 AML and advanced hematologic malignancies: results of a phase 1 dose escalation and expansion study. Abstract #725. Presented at the 2017 American Society of Hematology Annual Meeting, December 11, 2017; Atlanta, GA.