S78 patients with ND-AML had TP53 mutations. The ORR was 80% in ND-AML (TP53-mutated: 74%; TP53 wild-type: 93%); CR+CRi rates for TP53-mutated and TP53 wild-type patients were 63% and 86%. The ORR was 12% (N=2/17) in patients with R/RAML and prior VEN exposure (this cohort was closed for futility); the ORR in VEN-naïve R/R-AML was 67% (N=8/12). After median follow up of 9.2 months, mOS was not reached in patients with ND-AML (estimated 1-year OS TP53-mutated: 53%; TP53 wild-type: 83%). Median OS was 7.4 months in R/R-AML.7 Common AEs included febrile neutropenia (50%), pneumonia (38%), hyperbilirubinemia (11%), and transaminitis (11%); 24% of patients had ≥grade 3 anemia7. Four and 8-week mortality was 0% and 7%. Phase 3 studies are ongoing (NCT05079230). Conclusions Through incorporating molecularly or cellularly targeted therapies, further improvements in response rates and survival while maintaining tolerability appears feasible with AZA + VEN “triplets”. These regimens represent promising advances in the evolving and increasingly individualized AML treatment landscape. References 1. DiNardo CD, Jonas BA, Pullarkat V, Thirman MJ, Garcia JS, Wei AH, Konopleva M, Döhner H, Letai A, Fenaux P, Koller E. Azacitidine and venetoclax in previously untreated acute myeloid leukemia. New England Journal of Medicine. 2020 Aug 13;383(7):617-29. 2. Lachowiez CA, Loghavi S, Zeng Z, Tanaka T, Kim YJ, Uryu H, Turkalj S, Jakobsen NA, Luskin MR, Duose DY, Tidwell RS. A phase Ib/II study of ivosidenib with venetoclax+/-azacitidine in IDH1-mutated myeloid malignancies. Blood Cancer Discovery. 2023 Apr 27:BCD22. 3. Venugopal S, Takahashi K, Daver N, Maiti A, Borthakur G, Loghavi S, Short NJ, Ohanian M, Masarova L, Issa G, Wang X, Carlos BR, Yilmaz M, Kadia T, Andreeff M, Ravandi F, Konopleva M, Kantarjian HM, DiNardo CD. Efficacy and safety of enasidenib and azacitidine combination in patients with IDH2 mutated acute myeloid leukemia and not eligible for intensive chemotherapy. Blood Cancer J. 2022 Jan 25;12(1):10. doi: 10.1038/ s41408-021-00604-2. PMID: 35078972; PMCID: PMC8789767. 4. Atluri H, Maiti A, Sasaki K, Daver N, Alvarado Y, Hossain MF, Wang X, Pemmaraju N, Takahashi K, Borthakur G, Ferrajoli A. Phase Ib/2 Study of Oral Decitabine/ Cedazuridine (ASTX727) and Venetoclax in Combination with the Targeted Mutant IDH1 Inhibitor Ivosidenib or the Targeted Mutant IDH2 Inhibitor Enasidenib in IDH Mutated Acute Myeloid Leukemia. Blood. 2022 Nov 15;140(Supplement 1):6170-2. 5. Short N, DiNardo CD, Daver N, Macaron W, Yilmaz M, Borthakur G, Montalban-Bravo G, Garcia-Manero G, Issa GC, Sasaki K, Thompson PA. Updated Results from a Phase I/II Study of the Triplet Combination of Azacitidine, Venetoclax and Gilteritinib for Patients with FLT3-Mutated Acute Myeloid Leukemia. Blood. 2022 Nov 15;140(Supplement 1):2007-9. 6. Yilmaz M, Muftuoglu M, Kantarjian HM, Dinardo CD, Kadia TM, Konopleva M, Borthakur G, Pemmaraju N, Short NJ, Alvarado Valero Y, Maiti A. Quizartinib (QUIZ) with decitabine (DAC) and venetoclax (VEN) is active in patients (pts) with FLT3-ITD mutated acute myeloid leukemia (AML): A phase I/II clinical trial. 7. Daver N, Senapati J, Maiti A, Loghavi S, Kadia TM, DiNardo CD, Pemmaraju N, Jabbour E, MontalbanBravo G, Tang G, Sasaki K. Phase I/II Study of Azacitidine (AZA) with Venetoclax (VEN) and Magrolimab (Magro) in Patients (pts) with Newly Diagnosed (ND) Older/ Unfit or High-Risk Acute Myeloid Leukemia (AML) and Relapsed/Refractory (R/R) AML. Blood. 2022 Nov 15;140(Supplement 1):141-4.
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