FDA Approves Olutasidenib for IDH1-Mutated Relapsed/Refractory AML

FDA

The FDA has approved olutasidenib (Rezlidhia) capsules for adult patients with relapsed or refractory acute myeloid leukemia (AML) with a susceptible IDH1 mutation as detected by an FDA-approved test.¹

The regulatory decision was based on the phase 1/2 Study 2102-HEM-101 trial (NCT02719574), that included 147 adult patients with relapsed or refractory AML with an IDH1 mutation. Olutasidenib elicited a complete remission (CR) plus complete remission with partial hematologic recovery (CRh) rate of 35% (95% CI, 27%-43%), including 32% CR rate and 2.7% CRh rate. The median time to CR+CRh was 1.9 months (range, 0.9-5.6), and the median duration of CR+CRh was 25.9 months (95% CI, 13.5-not reached).

Additionally, among 86 patients who were red blood cell (RBC) and/or platelet transfusion dependent at baseline, 34% became RBC and platelet transfusion independent during any 56-day post-baseline period. Among 61 patients who were RBC/platelet transfusion independent at baseline, 64% remained transfusion independent during any 56-day post-baseline period.

The open-label, single-arm, multicenter Study 2102-HEM-101 trial enrolled 147 adult patients with relapsed/refractory AML with an IDH1 mutation confirmed using Abbott RealTime IDH1 Assay, which was also approved by the FDA.

Patients were required to have pathologically proven AML, except acute promyelocytic leukemia with the t(15;17) translocation, or intermediate- high-, or very high–risk myelodysplastic syndrome as defined by the World Health Organization criteria or Revised International Prognostic Scoring System.² Patients also needed to have disease that was relapsed or refractory to standard therapy and/or for which standard therapy is contraindicated or which has not adequately responded to standard therapy. Other inclusion criteria included a documented IDH1-R132 mutation, good performance status, and good kidney and liver function.

Key exclusion criteria included symptomatic central nervous system metastases or other tumor location, such as spinal cord compression, other compressive mass, uncontrolled painful lesion, or bone fracture, that necessitated urgent therapeutic intervention, palliative care, surgery or radiation therapy; congestive heart failure or unstable angina pectoris; previous history of myocardial infarction within 1 year prior to study entry, uncontrolled hypertension or uncontrolled arrhythmias; or active, uncontrolled bacterial, viral, or fungal infections requiring systemic therapy.

Enrolled patients received 150 mg of oral olutasidenib twice daily. Treatment continued until disease progression, unacceptable toxicity, or hematopoietic stem cell transplantation (HSCT).

The median treatment duration was 4.7 months (range, 0.1-26). Sixteen patients (11%) underwent HSCT following olutasidenib.

The primary end points of phase 2 of the study included CR+CRh rate and 4-month relapse-free survival (RFS). Secondary end points included time to response, duration of response, event-free survival, overall survival, and RFS.

The most common adverse effects occurring in at least 20% of patients included nausea, fatigue/malaise, arthralgia, constipation, leukocytosis, dyspnea, fever, rash, mucositis, diarrhea, and transaminitis.

References

1. FDA approves olutasidenib for relapsed or refractory acute myeloid leukemia with a susceptible IDH1 mutation. News release. FDA. December 1, 2022. Accessed December 1, 2022. https://bit.ly/3Vr284u
2. Open-label study of FT-2102 with or without azacitidine or cytarabine in patients with AML or MDS with an IDH1 mutation. ClinicalTrials.gov. Updated March 3, 2022. Accessed December 1, 2022. https://clinicaltrials.gov/ct2/show/NCT02719574