Differentiation Syndrome 

Revumenib can cause fatal or life-threatening differentiation syndrome (DS). Symptoms of differentiation syndrome, including those seen in patients treated with revumenib, include fever, dyspnea, hypoxia, peripheral edema, pleuropericardial effusion, acute renal failure, and/or hypotension.

In clinical trials, DS occurred in 39 (29%) of 135 patients treated with revumenib at the recommended dosage for relapsed or refractory acute leukemia with a KMT2A translocation, including 32% of patients with acute myeloid leukemia (AML), 25% of patients with mixed-phenotype acute leukemia (MPAL), and 14% of patients with acute lymphoblastic leukemia (ALL). DS was Grade 3 or 4 in 13% and fatal in one patient. The median time to onset was 10 days (range 3-41 days). Some patients experienced more than 1 DS event. Treatment interruption was required for 7% of patients, and treatment was withdrawn for 1% [see Adverse Reactions (6.1)].

Reduce the white blood cell count (WBC) to less than 25 Gi/L prior to starting revumenib. If DS is suspected, immediately initiate treatment with systemic corticosteroids (e.g., dexamethasone 10 mg intravenously every 12 hours in adults or dexamethasone 0.25 mg/kg/dose intravenously every 12 hours in pediatric patients weighing less than 40 kg) for a minimum of 3 days and until resolution of signs and symptoms. Institute supportive measures and hemodynamic monitoring until improvement. Interrupt REVUFORJ if severe signs and/or symptoms persist for more than 48 hours after initiation of systemic corticosteroids, or earlier if life-threatening symptoms occur such as pulmonary symptoms requiring ventilator support. Restart steroids promptly if DS recurs after tapering corticosteroids [see Dosage and Administration (2.3)].