The All-Oral Combination of Revumenib, Decitabine and Venetoclax for Relapsed or Refractory Acute Myeloid Leukemia (SAVE)
Mené sur 42 patients atteints d'une leucémie myéloïde aiguë refractaire ou récidivante (âge médian : 40 ans), cet essai de phase I/II détermine la dose maximale tolérée de révuménib (un inhibiteur ménine-KMT2A) en combinaison avec la décitabine et le vénétoclax puis évalue l'efficacité de cette combinaison du point de vue du taux de rémission complète
Purpose: Revumenib is an oral inhibitor of menin–KMT2A, a key dependency in acute myeloid leukemia (AML) with KMT2A rearrangement (KMT2Ar), NPM1 mutation (NPM1mt), or NUP98 rearrangement (NUP98r). Preclinical studies suggest synergy with BCL2 inhibition.
Patients and methods: In this phase 1–2 study, we evaluated an all-oral regimen of revumenib, decitabine/cedazuridine, and venetoclax in patients ≥12 years of age with relapsed or refractory AML. Decitabine/cedazuridine was given days 1-5, venetoclax days 1-14, and revumenib twice daily days 1-28. The primary objectives were to determine the recommended phase 2 dose (RP2D) and to assess efficacy according to the composite complete remission (CRc) rate.
Results: Forty-two patients were enrolled (median age, 40 years; range, 12-82) including 40% with KMT2Ar, 38% with NPM1mt, and 21% with NUP98r. Patients had a median of 2 prior lines of therapy; 52% had prior venetoclax. The RP2D of revumenib was 160 mg twice daily with a strong CYP3A4 inhibitor. Grade ≥3 adverse events included febrile neutropenia (36%), lung infection (21%), and thrombocytopenia (21%). Differentiation syndrome occurred in 10% (5% grade 3) and resolved with glucocorticoids.
The CRc rate was 71%, and the CR or complete remission with partial hematologic recovery (CR/CRh) rate was 60%, with measurable residual disease negativity by flow cytometry in 80% of these patients. The median duration of CR/CRh for all patients was 10.5 months, not reached in KMT2Ar, 10.7 months in NPM1mt, and 5.9 months in NUP98r. Emergent mutations in the menin-binding site occurred in 13%.
Conclusion: This combination was associated with high response rates and durable remissions, with an acceptable safety, in heavily pretreated patients with AML harboring alterations susceptible to menin inhibition.
Journal of Clinical Oncology , article en libre accès, 2026