On December 1, the U.S. Food and Drug Administration (FDA) 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. The FDA also approved the Abbott RealTime IDH1 Assay to select patients for treatment with olutasidenib.
Study 2102-HEM-101
Approval was based on Study 2102-HEM-101 (ClinicalTrials.gov identifier NCT02719574), an open-label, single-arm, multicenter clinical trial that included 147 adult patients with relapsed or refractory AML with an IDH1 mutation confirmed using the Abbott assay. 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 (range = 0.1–26 months). Sixteen (11%) patients underwent hematopoietic stem cell transplantation following olutasidenib.
Efficacy was established on the rate of complete remission plus complete remission with partial hematologic recovery, the duration of complete remission plus complete remission with partial hematologic recovery, and the rate of conversion from transfusion dependence to independence.
The complete remission plus complete remission with partial hematologic recovery rate was 35% (95% confidence interval [CI] = 27%–43%), including a complete remission rate of 32% and a complete remission with partial hematologic recovery rate of 2.7%. The median time to complete remission plus complete remission with partial hematologic recovery was 1.9 months (range = 0.9–5.6 months), and the median duration of complete remission plus complete remission with partial hematologic recovery was 25.9 months (95% CI = 13.5 months to not reached).
Among the 86 patients who were dependent on red blood cell and/or platelet transfusions at baseline, 29 (34%) became independent of red blood cell and platelet transfusions during any 56-day postbaseline period. Of the 61 patients who were independent of both red blood cell and platelet transfusions at baseline, 39 (64%) remained transfusion-independent during any 56-day postbaseline period.
The most common adverse reactions (≥ 20%) among patients taking olutasidenib 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.
The recommended olutasidenib dose is 150 mg taken orally twice daily on an empty stomach (at least 1 hour before or 2 hours after a meal) until disease progression or unacceptable toxicity. For patients without disease progression or unacceptable toxicity, treatment is recommended for a minimum of 6 months, allowing for clinical response.
