Warnings and Precautions for Revumenib (Revuforj)

Revumenib (trade name: Revuforj) is an oral targeted drug of the Menin inhibitor class, indicated for the treatment of relapsed or refractory acute leukemia with KMT2A gene rearrangement or NPM1 mutation. It is the first drug of this class to receive approval from the U.S. Food and Drug Administration (FDA).

Warnings and Precautions for Revumenib (Revuforj)

In clinical trials involving patients with relapsed/refractory KMT2A-rearranged acute leukemia or relapsed/refractory NPM1-mutated acute myeloid leukemia, the incidence of differentiation syndrome was 25% (60 out of 241 patients). Among these cases, the incidence of grade 3 or 4 differentiation syndrome was 12%, and two patients died as a result of this condition.

The median time to initial onset of differentiation syndrome was Day 9 after the start of treatment (range: 3 to 41 days). Following the onset of this syndrome, 7% of patients required treatment interruption and 1% required permanent discontinuation of treatment.

Symptoms of Differentiation Syndrome

Symptoms (observed in patients treated with Revuforj) may include:

Fever, dyspnea, hypoxemia, peripheral edema, pleural and pericardial effusion, acute renal failure, rash, hypotension.

Patients and their caregivers must be informed that if any of the above symptoms occur during treatment with Revuforj, they should contact their medical team immediately or go to the emergency department of the nearest hospital.

Dose Modifications for Adverse Reactions

In clinical trials, dose modifications due to adverse reactions were reported as follows:

Dose interruption: The incidence was 49%. The most common adverse reactions leading to dose interruption (incidence ≥5%) included prolonged QT interval on electrocardiogram, infection, febrile neutropenia, differentiation syndrome, nausea, and hypokalemia.

Dose reduction: The incidence was 12%. The most common adverse reaction leading to dose reduction (incidence ≥5%) was prolonged QT interval on electrocardiogram.

Permanent treatment discontinuation: The incidence was 20%. Adverse reactions leading to permanent treatment discontinuation (incidence >1%) included infection.