The FDA has granted approval to olutasidenib (Rezlidhia™, Rigel Pharmaceuticals Inc.) for treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) with a susceptible isocitrate dehydrogenase 1 gene (IDH1) mutation. Additionally, the FDA granted approval to the Abbott RealTime IDH1 Assay to accurately detect and select patients to receive olutasidenib. Olutasidenib is an inhibitor specific to mutant IDH1.
"Mutation of IDH1 occurs in 7% to 14% of patients with AML," wrote Justin M. Watts, MD, Chief of the Leukemia Section at the University of Miami Health System, and colleagues, in their publication of Study 2102-HEM-101 (NCT02719574), on which the approval was based. "Inhibition of mutant IDH1 in tumor cells and the subsequent reduction in 2-hydroxyglutarate production can restore normal cellular differentiation and provide therapeutic benefit in IDH1-mutated cancers."
Safety and efficacy were measured in the phase 1/2, multicenter, open-label, single-arm trial that included 147 patients with relapsed or refractory AML with a confirmed IDH1 mutation from the Abbott RealTime IDH1 Assay. Patients received 150 mg of olutasidenib orally twice a day until disease progression, unacceptable toxicity, or hematopoietic stem cell transplant. After a median treatment duration of 4.7 months, 11% of patients received hematopoietic stem cell transplant following treatment with olutasidenib.
The primary end points studied were rate of complete remission (CR) plus complete remission with partial hematologic recovery (CRh), the duration of CR plus CRh, and the time it took patients to go from transfusion dependence to independence. The rate of CR plus CRh was 35%, which included 32% of patients achieving CR and 2.7% achieving CRh. The median time it took to achieve CR plus CRh was 1.9 months, and the median duration of CR plus CRh was 25.9 months. For the 86 patients who were red blood cell and/or platelet transfusion–dependent, 34% became independent during any 56-day post-baseline period. Regarding the remaining 61 patients who were transfusion–independent at baseline, 64% remained transfusion-independent during any 56-day post-baseline period.
The most common adverse events occurring in ≥20% of those receiving olutasidenib were nausea, fatigue/malaise, arthralgia, constipation, leukocytosis, dyspnea, fever, rash, mucositis, diarrhea, and transaminitis. Included with the prescribing information is a Boxed Warning notifying the health care team and patients about the potential risk of differentiation syndrome, which can be fatal.
"Olutasidenib, with or without azacitidine, was well tolerated and showed meaningful clinical activity in patients with IDH1-mutated AML," concluded Dr. Watts and colleagues in their publication. "This study showed that olutasidenib has the potential to provide an additional treatment option for IDH1-mutated AML that might have a different therapeutic and safety profile than currently available treatments."
The recommended dose of olutasidenib is 150 mg taken orally twice daily on an empty stomach until disease progression or unacceptable toxicity. If the patient is not experiencing disease progression or unacceptable toxicity, it is recommended to treat for a minimum of six months to allow a clinical response.
For More Information
Watts JM, Baer MR, Yang J, et al (2022). Olutasidenib alone or with azacitidine in IDH1-mutated acute myeloid leukaemia and myelodysplastic syndrome: phase 1 results of a phase 1/2 trial. Lancet Haematol, [online ahead of print]. DOI:10.1016/S2352-3026(22)00292-7
Clinicaltrials.gov (2022). Open-label study of FT-2102 with or without azacitidine or cytarabine in patients with AML or MDS with an IDH1 mutation. NLM identifier: NCT02719574.
Rezlidhia™ (olutasidenib) prescribing information. Rigel Pharmaceuticals, Inc. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/215814s000lbl.pdf
US Food and Drug Administration (2022). FDA approves olutasidenib for relapsed or refractory acute myeloid leukemia with a susceptible IDH1 mutation. Available at: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-olutasidenib-relapsed-or-refractory-acute-myeloid-leukemia-susceptible-idh1-mutation?utm_medium=email&utm_source=govdelivery
Image credit: National Cancer Institute. Public domain.
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