Outcomes in Patients with Poor-Risk Cytogenetics with or without TP53 Mutations Treated with Venetoclax and Azacitidine

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

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;
Details: Publication Year 2022-12-15,Volume 28,Issue #24,Page 5272-5279
Journal Title: Clinical Cancer Research
Publication Type: Research article
Abstract: PURPOSE: To evaluate efficacy and safety of venetoclax + azacitidine in treatment-naive patients with acute myeloid leukemia harboring poor-risk cytogenetics and TP53mut or TP53wt. PATIENTS AND METHODS: We analyzed data from a phase III study (NCT02993523) comparing venetoclax (400 mg orally days 1-28) + azacitidine (75 mg/m2 days 1-7) or placebo + azacitidine, and from a phase Ib study (NCT02203773) of venetoclax + azacitidine. Patients were ineligible for intensive therapy. TP53 status was analyzed centrally; cytogenetic studies were performed locally. RESULTS: Patients (n = 127) with poor-risk cytogenetics receiving venetoclax + azacitidine (TP53wt = 50; TP53mut = 54) were compared with patients with poor-risk cytogenetics (n = 56) receiving azacitidine alone (TP53wt = 22; TP53mut = 18).For poor-risk cytogenetics + TP53wt patients, venetoclax + azacitidine versus azacitidine alone resulted in composite remission rates (CRc) of 70% versus 23%, median duration of remission (DoR) of 18.4 versus 8.5 months, and median overall survival (OS) of 23.4 versus 11.3 months, respectively. Outcomes with venetoclax + azacitidine were comparable with similarly treated patients with intermediate-risk cytogenetics and TP53wt.For poor-risk cytogenetics + TP53mut patients, venetoclax + azacitidine versus azacitidine alone resulted in CRc of 41% versus 17%, median DoR of 6.5 versus 6.7 months, and median OS of 5.2 versus 4.9 months, respectively.For poor-risk cytogenetics + TP53mut patients, predominant grade >/=3 adverse events (AE) for venetoclax + azacitidine versus 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 patients. CONCLUSIONS: In poor-risk cytogenetics + TP53mut patients, venetoclax + azacitidine improved remission rates but not DoR or OS compared with 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 with similarly treated patients with intermediate-risk cytogenetics. Toxicities were similar in TP53mut and TP53wt patients. See related commentary by Green and Zeidner, p. 5235.
Keywords: Humans; *Antineoplastic Combined Chemotherapy Protocols/adverse effects; Azacitidine/therapeutic use; Bridged Bicyclo Compounds, Heterocyclic/therapeutic use; Cytogenetic Analysis; *Leukemia, Myeloid, Acute/drug therapy/genetics; Mutation; Tumor Suppressor Protein p53/genetics; Treatment Outcome; Clinical Trials, Phase III as Topic; Clinical Trials, Phase I as Topic
Department(s): Haematology
PubMed ID: 36007102
Publisher's Version: https://doi.org/10.1158/1078-0432.CCR-22-1183
Open Access at Publisher's Site: https://doi.org/10.1158/1078-0432.Ccr-22-1183
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2025-02-20 06:41:22

Last Modified: 2025-02-20 06:42:28