Year: 2021
Type: article
Abstract: Background TP53 mutation (TP53mut) confers an adverse prognosis in acute myeloid leukemia (AML). Venetoclax with hypomethylating agents is a current standard for older patients; however, recent reports suggest that TP53mut confers resistance to venetoclax. The authors investigated the outcomes of patients with TP53mut AML who were treated with a 10‐day decitabine and venetoclax (DEC10‐VEN) (ClinicalTrials.gov identifier NCT03404193). Methods Patients with newly diagnosed AML received decitabine 20 mg/m2 for 10 days every 4 to 6 weeks for induction, followed by decitabine for 5 days after response. The venetoclax dose was 400 mg daily. TP53mut was identified in bone marrow samples using next‐generation sequencing, with sensitivity of 5%. Outcomes were analyzed according to European LeukemiaNet 2017 guidelines. Results Among 118 patients (median age, 72 years; age range, 49‐89 years), 63 (53%) had secondary AML, 39 (33%) had AML with complex karyotype, and 35 (30%) had TP53mut AML. The median TP53 variant allele frequency was 32% (interquartile range, 16%‐65%), 8 patients (23%) had only a single TP53 mutation, 15 (43%) had multiple mutations, and 12 (34%) had mutation and deletion. Outcomes were significantly worse in patients who had TP53mut AML compared with those who had wild‐type TP53 AML, with an overall response rate of 66% vs 89% (P = .002), a complete response/complete response with incomplete hematologic recovery rate of 57% vs 77% (P = .029), and a 60‐day mortality of 26% vs 4% (P < .001), respectively. Patients with TP53mut versus wild‐type TP53 had shorter overall survival at 5.2 versus 19.4 months, respectively (hazard ratio, 4.67; 95% CI, 2.44‐8.93; P < .0001), and shorter relapse‐free survival at 3.4 versus 18.9 months (hazard ratio, 4.80; 95% CI, 1.97‐11.69; P < .0001), respectively. Outcomes with DEC10‐VEN in patients with TP53mut AML were comparable to historical results with 10‐day decitabine alone. Conclusions Patients with TP53mut AML have lower response rates and shorter survival with DEC10‐VEN.
Source: Cancer
DOI: 10.1002/cncr.33689
Authors: Kunhwa Kim, Abhishek Maiti, Sanam Loghavi, Rasoul Pourebrahim, Tapan M. Kadia, Caitlin R. Rausch, Ken Furudate, Naval G. Daver, Yesid Alvarado, Maro Ohanian, Koji Sasaki, Nicholas J. Short, Koichi Takahashi, Musa Yilmaz, Guilin Tang, Farhad Ravandi, Hagop M. Kantarjian, Courtney D. DiNardo, Marina Y. Konopleva
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funders: Amgen, Eli Lilly and Company, Pfizer, AstraZeneca, Sanofi, American Society of Clinical Oncology, Celgene, FibroGen, Ablynx, Jazz Pharmaceuticals, Astex Pharmaceuticals, MEI Pharma, Agios Pharmaceuticals, Adaptive Biotechnologies, Syndax Pharmaceuticals, MacroGenics, Daiichi-Sankyo, Astellas Pharma, SymBio Pharmaceuticals Limited, Sun Pharma, National Institutes of Health, Genentech, University of Texas MD Anderson Cancer Center, National Cancer Institute, Daiichi Sankyo Europe
OpenAlex ID: W3177711368