Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2026
All-Oral Combination of Revumenib, Decitabine, and Venetoclax for Relapsed or Refractory AML (SAVE).
СтатьяКлиническое исследование I фазыКлиническое исследование II фазыНазвание и аннотация: Перевод в очереди
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Issa Ghayas C, Cuglievan Branko, El Hajjar Georgina, Jen Wei Ying, Bataller Alex, Short Nicholas J, DiNardo Courtney D, Alvarado Yesid, Loghavi Sanam, Duose Dzifa Yawa, Zhang Baili, Furudate Ken, Ning Jing, Xiao Lianchun, Mouhayar Elie, Pinto Alessandro, Bidikian Aram, Thompson Erika, Daver Naval, Garcia-Manero Guillermo, Farhat Aziz, McCall David, Kadia Tapan M, Abbas Hussein A, Tan Sheila, Bazinet Alexandre, Jabbour Elias, Montalban-Bravo Guillermo, Ravandi Farhad, Takahashi Koichi, Andreeff Michael, Kantarjian Hagop M
Аннотация
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.
METHODS: In this phase I-II study, we evaluated an all-oral regimen of revumenib, decitabine/cedazuridine, and venetoclax in patients 12 years and older with relapsed or refractory AML. Decitabine/cedazuridine was given on days 1-5, venetoclax on days 1-14, and revumenib twice daily on days 1-28. The primary objectives were to determine the recommended phase II 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 two 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.
METHODS: In this phase I-II study, we evaluated an all-oral regimen of revumenib, decitabine/cedazuridine, and venetoclax in patients 12 years and older with relapsed or refractory AML. Decitabine/cedazuridine was given on days 1-5, venetoclax on days 1-14, and revumenib twice daily on days 1-28. The primary objectives were to determine the recommended phase II 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 two 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.