Gangat Naseema, Elbeih Azeem, Ghosoun Nour, McCullough Kristen, Aperna Fnu, Johnson Isla M, Abdelmagid Maymona, Al-Kali Aref, Alkhateeb Hassan B, Begna Kebede H, Elliott Michelle, Mangaonkar Abhishek, Matin Aasiya, Saliba Antoine N, Hefazi Torghabeh Mehrdad, Litzow Mark R, Hogan William, Shah Mithun, Patnaik Mrinal M, Pardanani Animesh, Badar Talha, Murthy Hemant, Foran James, Palmer Jeanne, Sproat Lisa, Khera Nandita, Arana Yi Cecilia, Yates Samuel, Sneider Abigail, Dworkin Emily, Patel Anand A, Bazinet Alexandre, Senapati Jayastu, Bataller Alex, DiNardo Courtney, Kadia Tapan, Tefferi Ayalew
Division of Hematology, Mayo Clinic, Rochester, Minnesota, USA.
Division of Hematology, Mayo Clinic, Jacksonville, Florida, USA.
Am J Hematol. 2025 Feb;100(2):260-271. doi: 10.1002/ajh.27564. Epub 2024 Dec 13.
Patients with newly diagnosed acute myeloid leukemia (ND-AML) derive variable survival benefit from venetoclax + hypomethylating agent (Ven-HMA) therapy. The primary objective in the current study was to develop genetic risk models that are predictive of survival and are applicable at the time of diagnosis and after establishing treatment response. Among 400 ND-AML patients treated with Ven-HMA at the Mayo Clinic, 247 (62%) achieved complete remission with (CR) or without (CRi) count recovery. Multivariable analysis-derived hazard ratios (HR), including 1.8 for European LeukemiaNet (ELN) adverse karyotype, 4.7 for KMT2Ar, 1.7 for TP53 , 2.6 for KRAS , and 2.1 for IDH2 were applied to develop an HR-weighted risk model: low, intermediate, and high; respective median survival censored for allogeneic stem cell transplant (ASCT) (3-year survival) were "not reached" (67%), 19.1 (33%), and 7.1 months (0%). In patients achieving CR/CRi, adverse karyotype, KMT2Ar, KRAS , IDH2 predicted inferior survival, allowing for a complementary response-stratified risk model. The model was externally validated and was shown to be superior to the ELN 2024 risk model (AIC 179 vs. 195 and AUC 0.77 vs. 0.69). Survival was inferior with failure to achieve CR/CRi or not receiving ASCT; 3-year survival for high-risk with or without ASCT was 42% versus 0% (p < 0.01); intermediate 72% versus 43% (p = 0.06); and low-risk 88% versus 78% (p = 0.53). The Mayo genetic risk models offer pre-treatment and response-based prognostic tools for ND-AML treated with Ven-HMA. The current study underscores the prognostically indispensable role of achieving CR/CRi and ASCT.
新诊断的急性髓系白血病（ND-AML）患者从维奈克拉联合低甲基化药物（Ven-HMA）治疗中获得的生存益处各不相同。本研究的主要目的是建立基因风险模型，以预测生存率，并适用于诊断时及确定治疗反应后。在梅奥诊所接受Ven-HMA治疗的400例ND-AML患者中，247例（62%）实现了完全缓解（CR）或伴有（CR）或不伴有（CRi）血细胞计数恢复。多变量分析得出的风险比（HR），包括欧洲白血病网络（ELN）不良核型为1.8、KMT2Ar为4.7、TP53为1.7、KRAS为2.6、IDH2为2.1，用于建立一个HR加权风险模型：低、中、高；接受异基因干细胞移植（ASCT）（3年生存率）时各自的中位生存时间分别为“未达到”（67%）、19.1个月（33%）和7.1个月（0%）。在实现CR/CRi的患者中，不良核型、KMT2Ar、KRAS、IDH2预示着较差的生存率，从而产生了一个补充的反应分层风险模型。该模型经过外部验证，显示优于ELN 2024风险模型（AIC为179对195，AUC为0.77对0.69）。未实现CR/CRi或未接受ASCT的患者生存率较低；有或无ASCT的高危患者3年生存率分别为42%对0%（p<0.01）；中危患者为72%对43%（p=0.06）；低危患者为88%对78%（p=0.53）。梅奥基因风险模型为接受Ven-HMA治疗的ND-AML提供了基于治疗前和治疗反应的预后工具。当前研究强调了实现CR/CRi和ASCT在预后方面不可或缺的作用。
