Do Patients With TP53-Mutated AML Respond to Decitabine Plus Venetoclax?
Posted: Thursday, October 7, 2021
Research presented in the journal Cancer suggests that patients with acute myeloid leukemia (AML) who have a TP53 mutation may be more resistant to the combination of the hypomethylating agent decitabine and the BCL2 inhibitor venetoclax. Marina Y. Konopleva, MD, PhD, of MD Anderson Cancer Center, Houston, and colleagues sought to determine whether the activity of decitabine/venetoclax found in patients with adverse-risk disease in previous studies could be induced among patients with TP53 mutation, which is typically associated with a poor prognosis.
The study included 118 patients recently diagnosed with AML. A total of 35 patients (30%) had TP53-mutated disease. Among those patients, 8 (23%) had a single mutation, 15 (43%) had multiple mutations, and 12 (34%) had both a mutation and a deletion. All patients received 400 mg of daily venetoclax plus 10 days of 20 mg/m2 of decitabine for 4 to 6 weeks until induction and then an additional 5 days of decitabine following response.
Compared with those with wild-type TP53 disease, patients with TP53-mutated AML experienced substantially worse outcomes. For TP53-mutated disease versus wild-type TP53 disease, respectively, the overall response rate was 66% versus 89%, the complete response/complete response with incomplete hematologic recovery rate was 57% versus 77%, and the 60-day mortality rate was 66% versus 89%. In addition, overall survival and relapse-free survival were shorter for patients with TP53-mutated disease, at 5.2 months versus 19.4 months and 3.4 months versus 18.9 months, respectively.
“These results highlight the urgent need for novel therapies for [TP53-mutated acute myeloid leukemia],” concluded the authors.
Disclosure: For full disclosures of the study authors, visit acsjournals.onlinelibrary.wiley.com.