The FDA has approved olutasidenib capsules to treat patients with relapsed or refractory acute myeloid leukemia with identified an IDH1-mutation. The label comes with a boxed warning for differentiation syndrome, and a warning for hepatotoxicity.
The FDA has approved olutasidenib (Rezlidhia) capsules for the treatment of patients with relapsed or refractory acute myeloid leukemia (AML) with an identified IDH1-mutatuon by an FDA approved test. The FDA also approved Abbott RealTime IDH1 Assay to help identify patients eligible for olutasidenib.
The prescribing label comes with a box warning for differentiation syndrome, and a warning for hepatotoxicity.
The approval was supported by findings from the Study 2102-HEM-101 (NCT02719574), which showed that the rate of complete remission (CR) plus complete remission with partial hematologic recovery (CRh) was 35% (95% CI, 27%-43%) with olutasidenib; this included a CR rate of 32% and CRh rate of 2.7%. The median time to CR/CRh was 1.9 months (range, 0.9-5.6 months), and the median duration was 25.9 months (95% CI, 13.5-not reached).
Moreover, within a 56-day period, the drug inspired red blood cell (RBC) or platelet transfusion independency in 34% (n = 29) of 86 patients who were transfusion dependent at baseline. For the 61 patients who were transfusion independent at baseline, 64% (n = 39) maintained their independence throughout the 56-day post-baseline period.
Study 2102-HEM-101 was an open-label, single-arm, multicenter clinical rial which enrolled 146 patients with relapsed or refractory AML who had susceptible IDH1-mutations, according to the Abbot RealTime IDH1 Assay. Participants received the experimental agent twice a day, at 150-mg, until disease progression, unacceptable toxicity, or hematopoietic stem cell transplantation. The median treatment duration was 4.7 months (range, 0.1-26). A total of 16 patients (11%) underwent hematopoietic stem cell transplantation after receiving olutasidenib.
The most common adverse events (AEs) associated with olutasidenib included nausea fatigue/malaise, arthralgia, constipation, leukocytosis, dyspnea, fever, rash, mucositis, diarrhea, and transaminitis.
Differentiation syndrome can manifest as symptoms of dyspnea, pulmonary infiltrates/pleuropericardial effusion, kidney injury, hypotension, fever, and weight gain. In the clinical trial, differentiation syndrome occurred in 16% (n = 25) of patients, and grade 2 or 4 severity occurred in 8% of patients. Differentiation syndrome can occur as early as day 1 and up to 18 months following olutasidenib initiation.
The prescribing label also warns against hepatotoxicity; providers should monitor patient liver function during treatment, and monitor patients for signs of fatigue, anorexia, right upper abdominal discomfort, dark urine, or jaundice. If hepatotoxicity occurs, treatment should be interrupted, reduced, or discontinued, depending on the severity. In the trial, 23% of patients experienced hepatotoxicity, and 13% of patients experienced grade 3 or 4 hepatotoxicity. The median onset time was 1.2 months (range, 1 day-17.0 months) and the median time to resolution was 12 days (range, 1 day-17 months). The most common hepatotoxicities included elevated alanine aminotransferase, aspartate aminotransferase, blood alkaline phosphatase, and blood bilirubin.
The recommended dose is 150 mg orally twice daily. Doses should be taken at approximately at the same time every day, an both doses should not be taken within 8 hours of each other. Patients should be taught to take this medicine on an empty stomach, at least 1 before or 2 hours after a meal.