Food, Fungals, and Flexibility: Real-World Dosing of Revumenib

Caitlin Rausch, PharmD, BCOP, a leukemia pharmacist at MD Anderson Cancer Center with hands-on experience treating patients on the AUGMENT-101 trial, unpacks newly reported pharmacokinetic data for revumenib, the oral menin-KMT2A inhibitor approved for relapsed/refractory acute leukemia with a KMT2A rearrangement or a susceptible NPM1 mutation.

Rausch walks through how menin inhibitors work—freeing leukemia cells stuck in an arrested developmental state to differentiate and die, a mechanism tied directly to the drug's signature toxicity, differentiation syndrome—and frames revumenib's single-agent activity as a meaningful option for a historically high-risk, hard-to-treat population. The conversation grounds the discussion in why this PK analysis drew from the full 335-patient AUGMENT-101 population rather than a small dedicated substudy: a larger, more real-world dataset that includes patients on concomitant antifungals and antacids yields far more reliable conclusions than a handful of outlier-prone cases.

From there, Rausch translates the data into practical guidance. A low-fat meal modestly lowers revumenib exposure but not enough to justify an empty-stomach recommendation, and roughly half the patients on antacids, H2 blockers, or PPIs saw no exposure change at all, thanks to the drug's high solubility across the pH range. The real clinical lever, she explains, is CYP3A4 interaction potency: strong inhibitors like voriconazole roughly double exposure and require the reduced 160 mg dose, while moderate inhibitors like isavuconazole and fluconazole don't meaningfully change exposure and keep patients at the full 270 mg dose.

Rausch closes with counseling takeaways—the flexibility of twice-daily dosing around food and acid-reducing agents, the importance of patients flagging any new prescription or OTC medication to their leukemia team, and grapefruit juice as a standing CYP3A4 caveat—landing on drug-interaction vigilance as the one thing she wants every treating pharmacist to remember.