Revumenib-Induced QTc Prolongation Leading to Multiple Episodes of Torsades de Pointes and Ventricular Arrhythmias.

BACKGROUND

Revumenib is the only oral menin inhibitor approved for the treatment of relapsed/refractory acute leukemia with menin-lysine methyltransferase 2A (KMT2A) rearrangement in adults and pediatric patients aged >1 year. Revumenib was granted US Food and Drug Administration approval under the accelerated approval pathway, receiving both breakthrough therapy and orphan drug designations because of its potential to address a significant unmet need for patients with relapsed/refractory acute leukemia with a KMT2A translocation. While revumenib has no absolute contraindications, the package insert carries warnings, including the risk of corrected QT (QTc) prolongation.

CASE REPORT: A 76-year-old male with relapsed/refractory acute myeloid leukemia received revumenib after exhausting all other treatment options because of failure or intolerance. During treatment, the patient experienced multiple episodes of torsades de pointes and ventricular arrhythmias. Given the gravity of the patient's disease and the lack of alternative therapeutic options beyond hospice, a multidisciplinary team implemented aggressive measures to mitigate arrhythmic risk: placement of a permanent pacemaker following the initial torsades de pointes episode, meticulous electrolyte management, medication adjustments to limit QTc prolongation and drug-drug interactions, and use of a wearable cardioverter defibrillator. Despite a subsequent episode of torsades de pointes, the patient continued revumenib for an additional 29 days without further arrhythmias until discontinuation because of worsening acute myeloid leukemia shown by bone marrow biopsy.

CONCLUSION

Although current guidance recommends discontinuation of revumenib in the setting of life-threatening arrhythmias, this case highlights the importance of individualized risk-benefit assessment and supportive strategies when treatment is pursued as a last resort.