On December 1, 2022, the FDA approved olutasidenib (Rezlidhia; Forma Therapeutics) capsules, an oral IDH1 inhibitor, for adults with relapsed or refractory acute myeloid leukemia (AML) and a susceptible IDH1 mutation, as detected by an FDA-approved test.
On the same day, the FDA approved the Abbott RealTime IDH1 Assay to identify candidates for treatment with olutasidenib.
The FDA approval of olutasidenib was based on Study 2102-HEM-101, an open-label, single-arm, multicenter clinical trial that included 147 adult patients with relapsed or refractory AML and an IDH1 mutation, which was confirmed using the Abbott RealTime IDH1 Assay.
Patients received olutasidenib 50 mg twice daily orally until disease progression, unacceptable adverse events, or hematopoietic stem-cell transplantation. The median treatment duration was 4.7 months (range, 0.1-26 months), and 16 (11%) patients underwent a transplant after receiving olutasidenib.
Key efficacy measures were complete remission (CR) plus CR with partial hematologic recovery (CRh), the duration of CR+CRh, and conversion from transfusion dependence to independence.
The CR+CRh rate was 35% (95% confidence interval [CI], 27%-43%), including 32% CRs and 2.7% CRh. The median time to CR+CRh was 1.9 months (range, 0.9-5.6 months), and the median duration of CR+CRh was 25.9 months (95% CI, 13.5-not reached).
Of the 86 patients who were receiving red blood cell (RBC) and/or platelet transfusions at baseline, 29 (34%) became independent of RBC and/or platelet transfusions during any 56-day postbaseline. Of the 61 patients who were independent of RBC and/or platelet transfusions at baseline, 39 (64%) remained transfusion independent during any 56-day postbaseline.
The most common (≥20%) adverse events were nausea, fatigue/malaise, arthralgia, constipation, leukocytosis, dyspnea, fever, rash, mucositis, diarrhea, and transaminitis.
The prescribing information of olutasidenib contains a boxed warning about the risk of differentiation syndrome.
The recommended dose is 150 mg orally, taken twice daily ≥1 hour before or ≥2 hours after a meal, for at least 6 months to allow for response, or until disease progression or unacceptable side effects.