Precautions for Rezlidhia (Olutasidenib)

In clinical studies of Rezlidhia (olutasidenib) in the treatment of relapsed or refractory acute myeloid leukemia (AML), warnings and precautions such as differentiation syndrome and hepatotoxicity have emerged. If differentiation syndrome is suspected, stop Rezlidhia and start corticosteroid therapy and hemodynamic monitoring until symptoms disappear.

1. Differentiation syndrome:

In clinical trials,16% of patients developed differentiation syndrome, 8% of treated patients developed grade 3 or 4 differentiation syndrome, and 1% of patients died. Differentiation syndrome is associated with rapid proliferation and differentiation of myeloid cells and can be life-threatening or fatal, with symptoms including leukocytosis, dyspnea, pulmonary infiltrates/pleuropericardial effusion, renal impairment, pyrexia, edema, fever, and weight gain. Of the 25 patients who experienced differentiation syndrome, 76% recovered post-treatment or after dose interruption of Rezlidhia, which occurred as early as 1 day after initiation of Rezlidhia A treatment and up to 18 months, with or without leukocytosis observed.

If differentiation syndrome is suspected, Rezlidhia should be temporarily discontinued and systemic corticosteroids (eg, dexamethasone 10 mg intravenously every 12 hours) initiated for at least 3 days until signs and symptoms resolve. If concomitant leukocytosis is observed, initiate treatment with hydroxyurea as clinically indicated. The dosage of corticosteroids and hydroxyurea is gradually reduced after symptoms resolve. Premature discontinuation of corticosteroid and/or hydroxyurea therapy may result in recurrence of differentiation syndrome.

2. Hepatotoxicity:

Hepatotoxicity may manifest as elevated alanine aminotransferase(ALT), elevated aspartate aminotransferase (AST), elevated blood alkaline phosphatase, and/or elevated bilirubin. In clinical trials, 23% of patients experienced hepatotoxicity, with 13% experiencing grade 3 or 4 hepatotoxicity. One patient who received Rezlidhia in combination with azacitidine died from complications of drug-induced liver injury, a combination that was not applicable to Rezlidhia. The median time to onset of hepatotoxicity was 1.2 months after initiation of Rezlidhia treatment, and the median time to response was 12 days.

The most common liver toxicity is an increase in alanine aminotransferase, aspartate aminotransferase, blood alkaline phosphatase, and blood bilirubin. Doctors may need to monitor patients for clinical symptoms of abnormal liver function, such as fatigue, anorexia, right upper quadrant discomfort, dark urine, or jaundice. At the beginningBefore Rezlidhia, take it once a week for at least the first two months, every other week in the third month, once in the fourth month, and every other month during treatment. If liver function abnormalities occur, suspend, reduce, or permanently discontinue use of Rezlidhia, depending on recurrence/severity.

After Rezlidhia is approved for marketing, there is little information about its price and other related information. Please consult the medical consultant for details.