Shahswar Rabia, Gabdoulline Razif, Krueger Katja, Wichmann Martin, Götze Katharina S, Braitsch Krischan, Meggendorfer Manja, Schmalbrock Laura, Bullinger Lars, Modemann Franziska, Fiedler Walter, Krauter Juergen, Kaun Stephan, Rotermund Susanne, Voß Andreas, Behrens Yvonne Lisa, Bergmann Anke Katharina, Koller Elisabeth, Beutel Gernot, Thol Felicitas, Heidel Florian, Heuser Michael
Department of Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.
Department of Medicine III, Technical University of Munich (TUM) School of Medicine and Health, Munich, Germany.
Leukemia. 2025 Mar;39(3):614-622. doi: 10.1038/s41375-024-02501-6. Epub 2025 Jan 8.
Off-label hypomethylating agents and venetoclax (HMA/VEN) are often used for relapsed and refractory (R/R) AML patients. However, predictors of outcome are elusive. The objective of the current retrospective observational multicenter study of 240 adult patients (median age 68.6 years) with R/R AML was to establish a prognostic risk score. Overall response was documented in 106 (44%) patients. With a median follow-up of 31.5 months, 179 deaths were recorded. Median overall survival (mOS) was 7.9 months. In multivariate analysis of the subgroup with molecular information (n = 174), risk factors for inferior survival included the presence of extramedullary disease, HMA pretreatment and mutations in NF1, PTPN11, FLT3, and TP53, whereas mutated SF3B1 was identified as favorable risk factor. These risk factors were subsequently applied to construct an HR-weighted risk model that allocated patients to one of three risk groups with significantly different survival outcomes: favorable (n = 46; mOS 21.4 months), intermediate (n = 75; mOS 7.5 months), and adverse (n = 53; mOS 4.6 months; p < 0.001). The model was validated in 189 AML patients treated with HMA/VEN in first line. This clinical-molecular, 3-tiered venetoclax prognostic risk score (VEN-PRS) for HMA/VEN treatment outcomes in R/R AML patients will support the selection of appropriate treatment options in this high-risk population.
非标签使用的低甲基化药物和维奈克拉（HMA/VEN）常用于复发难治性（R/R）急性髓系白血病（AML）患者。然而，预后的预测因素尚不清楚。本项针对240例成年R/R AML患者（中位年龄68.6岁）的回顾性观察性多中心研究的目的是建立一个预后风险评分。106例（44%）患者记录到总体缓解。中位随访31.5个月，记录到179例死亡。中位总生存期（mOS）为7.9个月。在对有分子信息的亚组（n = 174）进行的多变量分析中，生存较差的危险因素包括髓外疾病的存在、HMA预处理以及NF1、PTPN11、FLT3和TP53的突变，而SF3B1突变被确定为有利的危险因素。随后应用这些危险因素构建了一个HR加权风险模型，该模型将患者分为三个生存结局有显著差异的风险组：低危（n = 46；mOS为21.4个月）、中危（n = 75；mOS为7.5个月）和高危（n = 53；mOS为4.6个月；p < 0.001）。该模型在189例一线接受HMA/VEN治疗的AML患者中得到验证。这个用于R/R AML患者HMA/VEN治疗结局的临床分子3层维奈克拉预后风险评分（VEN-PRS）将有助于在这一高危人群中选择合适的治疗方案。
