Revumenib

Two mechanisms converge on the kidney. (1) Forced leukemic differentiation triggers a differentiation syndrome (cytokine-release-like): fever, weight gain, capillary leak, pulmonary infiltrates, edema and hypotension producing pre-renal azotemia. (2) Rapid lysis of a high leukemic burden causes tumor lysis syndrome — hyperuricemia, hyperphosphatemia and hyperkalemia with intratubular uric-acid and calcium-phosphate crystal precipitation plus renal vasoconstriction, causing crystalline AKI. Hypocalcemia and QTc-relevant electrolyte shifts accompany TLS. There is no direct tubular toxin.

Differentiation syndrome: dyspnea, fever, peripheral/pulmonary edema, hypotension, rising creatinine and rising leukocyte count. TLS: hyperuricemia, hyperkalemia, hyperphosphatemia, hypocalcemia with AKI. Monitor the QTc.

During early treatment as leukemic differentiation and lysis occur (first days–weeks).

Oral small-molecule inhibitor of the protein–protein interaction between menin and KMT2A (MLL), disrupting the menin-dependent transcriptional complex that sustains HOX/MEIS1 leukemogenic programs in KMT2A-rearranged and NPM1-mutant acute leukemias, thereby inducing leukemic-cell differentiation. Approved for KMT2A-rearranged relapsed/refractory acute leukemia.

Differentiation syndrome: corticosteroids (e.g., dexamethasone), diuresis for fluid overload, supportive care, and drug interruption if severe. TLS: IV hydration, rasburicase for hyperuricemia, electrolyte correction (treat hyperkalemia/hyperphosphatemia, cautious calcium), and renal replacement therapy if refractory.