Mayo Genetic Risk Models for Newly Diagnosed Acute Myeloid Leukemia Treated With Venetoclax + Hypomethylating Agent
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 <sup>MUT</sup>, 2.6 for KRAS <sup>MUT</sup>, and 2.1 for IDH2 <sup>WT</sup> 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 <sup>MUT</sup>, IDH2 <sup>WT</sup> 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.
Authors
- Naseema Gangat (ORCID: https://orcid.org/0000-0002-9104-6172)
- Antoine N. Saliba (ORCID: https://orcid.org/0000-0001-5134-7336)
- Cecilia Y. Arana Yi (ORCID: https://orcid.org/0000-0002-7441-5140)
- Aref Al‐Kali (ORCID: https://orcid.org/0000-0002-0824-3715)
- Courtney Denton Dinardo (ORCID: https://orcid.org/0000-0001-9003-0390)
- Abhishek Avinash Mangaonkar (ORCID: https://orcid.org/0000-0003-2458-9887)
- Emily Dworkin
- Ayalew Tefferi (ORCID: https://orcid.org/0000-0003-4605-3821)
- Isla McKerrow Johnson (ORCID: https://orcid.org/0000-0002-3290-5213)
- Maymona Abdelmagid
- Tapan Mahendra Kadia (ORCID: https://orcid.org/0000-0002-9892-9832)
- Mithun Vinod Shah (ORCID: https://orcid.org/0000-0002-5359-336X)
- Hemant S. Murthy (ORCID: https://orcid.org/0000-0003-4534-4248)
- Animesh Dev Pardanani (ORCID: https://orcid.org/0000-0002-9084-4148)
- Álex Bataller (ORCID: https://orcid.org/0000-0002-6085-2745)
- James M. Foran (ORCID: https://orcid.org/0000-0003-1673-1708)
- Abigail Sneider (ORCID: https://orcid.org/0000-0002-8119-3654)
- Anand Patel (ORCID: https://orcid.org/0000-0002-0296-8686)
- Aasiya Matin (ORCID: https://orcid.org/0000-0001-6807-0871)
- Samuel J. Yates (ORCID: https://orcid.org/0000-0003-0483-2560)
- Jeanne Palmer (ORCID: https://orcid.org/0000-0002-2185-1504)
- Nandita Khera (ORCID: https://orcid.org/0000-0002-0577-3155)
- Alexandre Bazinet (ORCID: https://orcid.org/0000-0001-5538-4943)
- Michelle Ann Elliott (ORCID: https://orcid.org/0000-0002-7366-9886)
- Hassan B. Alkhateeb (ORCID: https://orcid.org/0000-0002-3609-8404)
- Mehrdad Hefazi (ORCID: https://orcid.org/0000-0001-8860-3380)
- Mrinal M. Patnaik (ORCID: https://orcid.org/0000-0001-6998-662X)
- Kristen Beth McCullough (ORCID: https://orcid.org/0000-0003-4252-2619)
- Talha Badar (ORCID: https://orcid.org/0000-0003-1548-918X)
- Jayastu Senapati (ORCID: https://orcid.org/0000-0002-6831-2567)
- Kebede H. Begna (ORCID: https://orcid.org/0000-0003-2730-8593)
- William J. Hogan (ORCID: https://orcid.org/0000-0002-5841-4105)
- Mark Robert Litzow (ORCID: https://orcid.org/0000-0002-9816-6302)
- Fnu Aperna
- Lisa Sproat
- Azeem Elbeih
- Nour Ghosoun
Institutions
- Mayo Clinic (US)
- The University of Texas MD Anderson Cancer Center (US)
- Jacksonville College (US)
- WinnMed (US)
- University of Chicago (US)
- Mayo Clinic in Arizona (US)
- Mayo Clinic in Florida (US)
Publication Details
- Journal
- American Journal of Hematology
- Published
- 2024-12-13
- DOI
- https://doi.org/10.1002/ajh.27564
- Citations
- 22
- Primary Topic
- Acute Myeloid Leukemia Research
- Type
- article
- Field-Weighted Citation Impact
- 10.00