FDA Approves Olutasidenib for Patients With Relapsed/Refractory IDH1-Mutant AML

On December 1, 2022, the Food and Drug Administration (FDA) approved olutasidenib (Rezlidhia; Forma Therapeutics, Inc) capsules for adult patients with relapsed or refractory acute myeloid leukemia (AML) with a susceptible IDH1 mutation, as detected by an FDA-approved test. At the same time, the FDA approved the Abbott RealTime IDH1 Assay test to select patients eligible for olutasidenib.

This approval was based on an open-label, single-arm, multicenter clinical trial, Study 2102-HEM-101. The study included 147 adult patients with relapsed/refractory AML with an IDH1 mutation confirmed using the Abbott RealTime IDH1 Assay. In the trial, olutasidenib was given orally at 150 mg twice daily until disease progression, unacceptable toxicity, or hematopoietic stem cell transplantation. The median treatment duration was 4.7 months, with a range of 0.1 to 26 months. Overall, there were 16 (11%) patients who underwent hematopoietic stem cell transplantation following olutasidenib.

Efficacy was established on the rate of complete remission (CR) plus complete remission with partial hematologic recovery (CRh), the duration of CR+CRh, and the rate of conversion from transfusion dependence to independence. The CR+CRh rate was 35% (95% confidence interval [CI], 27% to 43%), including 32% CR and 2.7% CRh. The median time to CR+CRh was 1.9 months with a range of 0.9 to 5.6 months, and the median duration of CR+CRh was 25.9 months (95% CI, 13.5 months to not reached).

Among the 86 patients who were dependent on red blood cell (RBC) and/or platelet transfusions at baseline, 29 (34%) became independent of RBC and platelet transfusions during a 56-day post-baseline period. Of the 61 patients who were independent of both RBC and platelet transfusions at baseline, 39 (64%) remained transfusion independent during a 56-day post-baseline period.

The most common adverse reactions (≥20%) were nausea, fatigue/malaise, arthralgia, constipation, leukocytosis, dyspnea, fever, rash, mucositis, diarrhea, and transaminitis. The prescribing information contains a “Boxed Warning” alerting health care professionals and patients about the risk of differentiation syndrome, which can be fatal.

Source:

FDA approves olutasidenib for relapsed or refractory acute myeloid leukemia with a susceptible IDH1 mutation. Press Release. The US Food and Drug Administration. Published online December 1, 2022. Accessed December 5, 2022. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-olutasidenib-relapsed-or-refractory-acute-myeloid-leukemia-susceptible-idh1-mutation