Outcomes in patients with poor-risk cytogenetics with or without TP53 mutations treated with venetoclax and azacitidine
- Author(s)
- Pollyea, DA; Pratz, KW; Wei, AH; Pullarkat, V; Jonas, BA; Recher, C; Babu, S; Schuh, AC; Dail, M; Sun, Y; Potluri, J; Chyla, B; DiNardo, CD;
- Journal Title
- Clinical Cancer Research
- Publication Type
- epub ahead of print
- Abstract
- PURPOSE: Evaluate efficacy and safety of venetoclax+azacitidine in treatment-naïve patients with AML harboring poor-risk cytogenetics and TP53mut or TP53wt. PATIENTS AND METHODS: We analyzed data from a phase-3 study (NCT02993523) comparing venetoclax (400 mg orally days 1-28)+azacitidine (75 mg/m2 days 1-7) or placebo+azacitidine, and a phase-1b study (NCT02203773) of venetoclax+azacitidine. Patients were ineligible for intensive therapy. TP53 status was analyzed centrally; cytogenetic studies were performed locally. RESULTS: 127 patients with poor-risk cytogenetics receiving venetoclax+azacitidine (TP53wt=50; TP53mut=54) were compared to 56 patients with poor-risk cytogenetics receiving azacitidine alone (TP53wt=22; TP53mut=18). For poor-risk cytogenetics+TP53wt, venetoclax+azacitidine vs. azacitidine alone resulted in composite remission rates (CRc) of 70% vs. 23%, median DoR of 18.4 vs. 8.5 months, and median OS of 23.4 vs. 11.3 months, respectively. Outcomes with venetoclax+azacitidine were comparable to similarly-treated patients with intermediate-risk cytogenetics+TP53wt. For poor-risk cytogenetics+TP53mut, venetoclax+azacitidine vs. azacitidine alone resulted in CRc of 41% vs. 17%, median DoR of 6.5 vs. 6.7 months, and median OS of 5.2 vs. 4.9 months, respectively. For poor-risk cytogenetics+TP53mut, predominant grade ≥3 adverse events (AEs) for venetoclax+azacitidine/azacitidine were febrile neutropenia (55%/39%), thrombocytopenia (28%/28%), neutropenia (26%/17%), anemia (13%/6%), and pneumonia (28%/33%). AEs were comparable between TP53mut and TP53wt. CONCLUSIONS: In poor-risk cytogenetics+TP53mut patients, venetoclax+azacitidine improved remission rates but not DoR or OS compared to azacitidine alone. However,in poor-risk cytogenetics+TP53wt patients, venetoclax + azacitidine resulted in higher remission rates and longer DoR and OS than azacitidine alone, with outcomes comparable to similarly-treated patients with intermediate-risk cytogenetics. Toxicities were similar in TP53mut and TP53wt patients.
- Publisher
- AACR
- Research Division(s)
- Blood Cells And Blood Cancer
- PubMed ID
- 36007102
- Publisher's Version
- https://doi.org/10.1158/1078-0432.Ccr-22-1183
- Open Access at Publisher's Site
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Creation Date: 2022-08-30 09:11:31
Last Modified: 2022-08-30 09:20:03