On December 1, 2022, the U.S. Food and Drug Administration (FDA) approved olutasidenib (Rezlidhia®) capsules for adult patients with relapsed or refractory acute myeloid leukemia (AML) with susceptible IDH1 variants as detected by an FDA-approved test. FDA also approved the Abbott RealTime IDH1 Assay to identify patients who are appropriate for olutasidenib.

FDA Approves Olutasidenib for Relapsed or Refractory Acute Myeloid Leukemia With Susceptible IDH1 Variants

Approval was based on the 2102-HEM-101 (NCT02719574) study, an open-label, single-arm, multicenter clinical trial of 147 adult patients with relapsed or refractory AML with an IDH1 variant confirmed with the assay. Patients received 150 mg of oral olutasidenib twice daily until they experienced disease progression, unacceptable toxicity, or a need for hematopoietic stem cell transplantation, with a median treatment duration of 4.7 months (range = 0.1–26 months). Sixteen (11%) patients underwent hematopoietic stem cell transplantation following olutasidenib.

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

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

The most common adverse reactions reported in at least 20% of patients treated with olutasidenib were nausea, fatigue or malaise, arthralgia, constipation, leukocytosis, dyspnea, fever, rash, mucositis, diarrhea, and transaminitis. Olutasidenib’s prescribing information contains a boxed warning alerting healthcare professionals and patients about risk for potentially fatal differentiation syndrome

The recommended olutasidenib dose is 150 mg, orally twice daily on an empty stomach at least one hour before or two hours after a meal, until patients experience disease progression or unacceptable toxicity. Patients who do not experience disease progression or unacceptable toxicity should continue treatment for a minimum of six months to determine clinical response.

View the full prescribing information for olutasidenib.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 800-FDA-1088.

For assistance with single-patient investigational new drug applications, contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.