Treatment outcomes for newly diagnosed, treatment-naïve TP53-mutated acute myeloid leukemia: a systematic review and meta-analysis

作者：Naval Daver, Shahed Iqbal, Camille Renard, Rebecca J. Chan, Ken Hasegawa, Hao Hu, Preston Tse, Jiajun Yan, Michael J. Zoratti, Feng Xie, Giridharan Ramsingh · 发表于：Journal of Hematology & Oncology · 年份：2023 · DOI：10.1186/s13045-023-01417-5 · 被引用次数：72 · 研究领域：Acute Myeloid Leukemia Research、Protein Degradation and Inhibitors、Chronic Myeloid Leukemia Treatments

BACKGROUND: TP53 mutations, which are present in 5% to 10% of patients with acute myeloid leukemia (AML), are associated with treatment resistance and poor outcomes. First-line therapies for TP53-mutated (TP53m) AML consist of intensive chemotherapy (IC), hypomethylating agents (HMA), or venetoclax combined with HMA (VEN + HMA). METHODS: We conducted a systematic review and meta-analysis to describe and compare treatment outcomes in newly diagnosed treatment-naïve patients with TP53m AML. Randomized controlled trials, single-arm trials, prospective observational studies, and retrospective studies were included that reported on complete remission (CR), CR with incomplete hematologic recovery (CRi), overall survival (OS), event-free survival (EFS), duration of response (DoR), and overall response rate (ORR) among patients with TP53m AML receiving first-line treatment with IC, HMA, or VEN + HMA. RESULTS: Searches of EMBASE and MEDLINE identified 3006 abstracts, and 17 publications describing 12 studies met the inclusion criteria. Random-effects models were used to pool response rates, and time-related outcomes were analyzed with the median of medians method. IC was associated with the greatest CR rate of 43%, and CR rates were 33% for VEN + HMA and 13% for HMA. Rates of CR/CRi were comparable for IC (46%) and VEN + HMA (49%) but were lower for HMA (13%). Median OS was uniformly poor across treatments: IC, 6.5 months; VEN + HMA, 6.2 months; and HMA, 6.1 months. For IC, the EFS es...