Olutasidenib Gains FDA Approval for IDH1-Mutated Relapsed/Refractory Acute Myeloid Leukemia

The FDA granted approval to olutasidenib (Rezlidhia) capsules for the treatment of adults with relapsed or refractory acute myeloid leukemia (AML) with a susceptible IDH1 mutation detected by an FDA-approved test.¹

The approval was based on the results of the open-label, single-arm, multicenter, phase 1/2 Study 2102-HEM-101 trial (NCT02719574). The trial enrolled 147 adults with relapsed or refractory AML with an IDH1 mutation confirmed using the Abbott RealTime IDH1 Assay, which the FDA also approved. Inclusion criteria required patients to have pathologically proven AML, except acute promyelocytic leukemia with t(15;17) translocation, or intermediate-, high-, or very high–risk myelodysplastic syndrome defined by World Health Organization criteria or Revised International Prognostic Scoring System.²

Enrolled patients also needed to have disease that was relapsed or refractory to standard therapy and/or for whom standard therapy is contraindicated or who didn’t adequately respond to standard therapy. Other criteria for inclusion were a documented IDH1-R132 mutation, good performance status, and good kidney and liver function.

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 requiring urgent therapeutic intervention, palliative care, surgery or radiation therapy; congestive heart failure or unstable angina pectoris; previous history of myocardial infarction within a year before study entry, uncontrolled hypertension or uncontrolled arrhythmias; or active, uncontrolled bacterial, viral, or fungal infections necessitating systemic therapy.

Patients enrolled in the trial were administered 150 mg of oral olutasidenib twice daily. Treatment continued until disease progression, unacceptable toxicity, or hematopoietic stem cell transplantation (HSCT). Median treatment duration was 4.7 months (range, 0.1-26) and 16 patients (11%) underwent HSCT following treatment with olutasidenib.

The primary end points for phase 2 of Study 2102-HEM-101 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.

Treatment with olutasidenib produced a complete remission (CR) plus CR with partial hematologic recovery (CRh) rate of 35% (95% CI, 27%-43%), including 32% CR rate and 2.7% CRh rate. Median time to CR+CRh was 1.9 months (range, 0.9-5.6), with a median duration of CR+CRh of 25.9 months (95% CI, 13.5-not reached).

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 of the 56-day post-baseline period. In 61 patients who were RBC/platelet transfusion independent at baseline, 64% were transfusion independent during any of the 56-day post-baseline period.

The most common adverse effects observed 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