Session: 615. Acute Myeloid Leukemias: Clinical and Epidemiological: Poster II
Hematology Disease Topics & Pathways:
Acute Myeloid Malignancies, AML, Diseases, Myeloid Malignancies
Methods: We screened adult pts treated at our center for newly diagnosed AML between January 2012 and December 2023. We identified 396 pts (18%) with NPM1mt and 1819 pts (82%) with NPM1wt. The composite complete remission or complete remission with incomplete hematologic recovery (CRc) was identified by subgroup, and MRD was assessed by flow cytometry (sensitivity: 10-4). Event-free survival (EFS) was defined as the duration from the initiation of treatment until the earliest occurrence of disease relapse, disease progression, death from any cause, or failure of achieving a response (FDA Definition, i.e. event at day 0), with overall survival (OS) defined as the duration from therapy start to death or last follow-up. Predictors of survival were identified using Cox regression where factors with P<0.1 on univariate analysis were selected for multivariate analysis (MVA).
Results: Compared with NPM1wt AML, pts with NPM1mt were more commonly female (56% vs 43%; P<0.001) and had significantly higher bone marrow blasts at diagnosis (P<0.001). Those with NPM1mt more commonly had a monocytic phenotype (27% vs 9%, P<0.001), a diploid karyotype (75% vs 24%, P<0.001), and myelofibrosis (MF-1 or higher) (30% vs 23%, P=0.008). Extramedullary disease (EMD) had similar incidence in both groups (3.5% vs 2.4%; P=0.2). Most common co-occurring mutations included DNMT3A (47% vs 18%, P<0.001), FLT3-ITD (42% vs 13%, P<0.001), KRAS/NRAS (29% vs 25%, P=0.2), SRSF2 (23% vs 28%, P=0.4) and TET2 (22% vs 14%, P<0.001). Therapy-related AML was 9% of NPM1mt vs 19% of NPM1wt AML (P<0.001). There were 16 pts (4%) with NPM1mt and an adverse karyotype; 44 pts (11%) had NPM1mt and co-occurring adverse risk mutations.
High intensity chemotherapy (HIC) was given for 190 NPM1mt pts (48%), of which 46 pts (12%) had the addition of venetoclax (HIC+Ven), whereas 66 pts (17%) received a hypomethylating agent + Ven (HMA+Ven), 32 pts (8%) received cladribine with low-dose cytarabine + Ven (Clad LDAC Ven) and 106 pts (27%) received other lower-intensity treatments.
The CRc rate for those with NPM1mt who received HIC without ven was 94% vs 96% for HIC+Ven, with MRD-neg rates of 86% and 82% respectively. Those with NPM1mt who received HMA+Ven had a CRc rate of 86%, whereas Clad LDAC Ven led to a 94% rate (MRD neg of 96% and 97% respectively).
With a median follow-up of 52.6 months, NPM1mt pts treated with HIC had a median EFS and OS of 87.8 and 87.8 months with 2-year rates of 63% and 65%, respectively. NPM1mt pts treated with Clad LDA Ven had a median EFS and OS of 59.6 and 59.6 months with 2-year rates of 73% and 76% respectively. HMA+ven in NPM1mt (all of whom were >60 years) led to a median EFS and OS of 15.4 and 23.6 months, with 2-year rates of 48% and 51% respectively. In those with NPM1mt and age>75 years, the median EFS and OS were 10.3 months and 10.9 months, with 2-year rates of 32% and 32% respectively.
Among pts with NPM1mt who received HIC, predictors of worse EFS and OS in MVA included age [Hazard ratio (HR) for OS: 1.03; P=0.009], FLT3-ITD (HR for OS: 1.92; P=0.014), EMD (HR for OS: 6.03; P=0.001), and a performance status > 2 (HR for OS: 8.01; P=0.001). The addition of venetoclax to HIC did not independently predict for outcomes. Among pts with NPM1mt who received HMA+Ven, the only predictor of worse EFS and OS was age (HR for OS: 1.10; P=0.016). Notably, therapy-related status or adverse risk features by ELN did not predict outcomes.
Conclusion: In conclusion, older age, worse performance status, FLT3-ITD co-mutation, and EMD predicted for worse outcomes in NPM1mt AML treated with HIC whereas older age was the only predictor of outcomes in those receiving HMA + venetoclax.
Disclosures: Kantarjian: AbbVie, Amgen, Ascentage, Ipsen Biopharmaceuticals, KAHR Medical, Novartis, Pfizer, Shenzhen Target Rx, Stemline,Takeda: Consultancy, Honoraria. Sasaki: Daiichi-Sankyo: Consultancy; Enliven: Research Funding; Otsuka: Other: Lecture fees; Chugai: Other: Lecture fees; Novartis: Consultancy, Research Funding; Pfizer: Consultancy. Short: Novartis: Honoraria; Takeda Oncology: Honoraria, Research Funding; BeiGene: Honoraria; Sanofi: Honoraria; Autolus: Honoraria; GSK: Consultancy, Research Funding; Amgen: Honoraria; Pfizer Inc.: Honoraria; NextCure: Research Funding; Adaptive Biotechnologies: Honoraria; Stemline Therapeutics: Research Funding; Xencor: Research Funding; Astellas Pharma, Inc.: Honoraria, Research Funding. Cuglievan: Kura Oncology: Research Funding; Syndax Pharmaceuticals, Inc.: Other: travel, accommodations, Research Funding; LLS: Research Funding; Octapharma: Other: travel, accommodations, research. Loghavi: Pathology Education Partners; VJ HemeOnc, College of American Pathologists, OncLive, ICCS, MD Education, NCCN, MashUp Media, NCTN, Aptitude Health: Honoraria; Guidepoint; QualWorld; Gerson Lehrman Group, AlphaSight, Arima, Qiagen, Opinion Health: Consultancy; Astellas, Amgen: Research Funding; Abbvie: Current holder of stock options in a privately-held company; Syndx, Servier, BMS: Membership on an entity's Board of Directors or advisory committees; Abbvie, Daiichi Sankyo, BluePrint Medicine, Caris Diagnostics, Recordati, Servier: Consultancy. Yilmaz: daiichi sankyo: Honoraria, Research Funding. Montalban-Bravo: Rigel: Research Funding; Takeda: Research Funding. Pemmaraju: Protagonist Therapeutics: Consultancy; Celgene: Honoraria, Other: Travel Expenses; Cellectis: Research Funding; Incyte: Honoraria; CTI BioPharma: Consultancy; Pacylex: Consultancy; Bristol-Myers Squibb: Consultancy; Aptitude Health: Honoraria; Roche Molecular Diagnostics: Honoraria; Novartis: Honoraria, Research Funding; Immunogen: Consultancy; LFB Biotechnologies: Honoraria; CareDx: Honoraria; Mustang Bio: Honoraria, Other: Travel Expenses, Research Funding; Springer Science + Business Media: Honoraria; Neopharm: Honoraria; ClearView Healthcare Partners: Consultancy; Stemline Therapeutics: Honoraria, Other: Travel Expenses, Research Funding; DAVA Oncology: Honoraria, Other: Travel Expenses; Affymetrix/Thermo Fisher Scientific: Research Funding; Blueprint Medicines: Consultancy, Honoraria; Triptych Health Partners: Consultancy; Daiichi Sankyo: Research Funding; Plexxikon: Research Funding; Samus Therapeutics: Research Funding; Blueprint Medicines OncLive PeerView Institute for Medical Education: Consultancy, Other: advisory board; Astellas: Consultancy; AbbVie: Honoraria, Other: Travel Expenses, Research Funding; ASH Committee on Communications ASCO Cancer.NET Editorial Board: Other: Leadership; Karger Publishers: Other: Licenses; National Institute of Health/National Cancer Institute (NIH/NCI): Research Funding; HemOnc Times/Oncology Times: Other: uncompensated. Daver: Novimmune: Research Funding; Arog: Consultancy; Celgene: Consultancy; Servier: Consultancy, Research Funding; Agios: Consultancy; FATE Therapeutics: Other: Consulting Fees, Research Funding; Trillium: Consultancy, Research Funding; Trovagene: Research Funding; Menarini Group: Consultancy; Shattuck Labs: Consultancy; Gilead: Consultancy, Research Funding; Jazz: Consultancy; Hanmi: Research Funding; KITE: Research Funding; Novartis: Consultancy; Syndax: Consultancy; Astellas: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy, Research Funding; Daiichi-Sankyo: Consultancy, Research Funding; Glycomimetics: Research Funding. Ravandi: Abbvie: Consultancy, Honoraria; Xencor: Research Funding; Amgen: Research Funding; Syros: Consultancy, Honoraria, Research Funding; Astellas: Consultancy, Honoraria; Prelude: Consultancy, Honoraria, Research Funding; Syndax: Honoraria; BMS: Consultancy, Honoraria; Astyex/Taiho: Research Funding. Jabbour: AbbVie, Adaptive Biotechnologies, Amgen, Astellas Pharma, BMS, Genentech, Incyte, Pfizer, Takeda: Consultancy; AbbVie, Adaptive Biotechnologies, Amgen, Ascentage Pharma Group, Pfizer, Takeda: Research Funding. Kadia: Sellas: Consultancy, Research Funding; Amgen: Research Funding; Incyte: Research Funding; ASTEX: Research Funding; Ascentage: Research Funding; DrenBio: Consultancy, Research Funding; Pfizer: Research Funding; Novartis: Honoraria; Abbvie: Consultancy, Research Funding; Rigel: Honoraria; BMS: Consultancy, Research Funding; Regeneron: Research Funding; AstraZeneca: Research Funding; Genentech: Consultancy, Research Funding; JAZZ: Research Funding; Servier: Consultancy; Cellenkos: Research Funding. Borthakur: Catamaran Bio, AbbVie, PPD Development, Protagonist Therapeutics, Janssen: Consultancy; Astex Pharmaceuticals, Ryvu, PTC Therapeutics: Research Funding; Pacylex, Novartis, Cytomx, Bio Ascend: Membership on an entity's Board of Directors or advisory committees. Garcia-Manero: Bristol Myers Squibb: Other: Personal fees, Research Funding; Curis: Research Funding; Forty Seven: Research Funding; Merck: Research Funding; Genentech: Research Funding; Janssen: Research Funding; Astex: Research Funding; Onconova: Research Funding; AbbVie: Research Funding; Helsinn: Research Funding; Novartis: Research Funding; H3 Biomedicine: Research Funding; Aprea: Research Funding; Astex: Other: Personal fees; Helsinn: Other: Personal fees; Genentech: Other: Personal fees; Amphivena: Research Funding. DiNardo: Loxo: Research Funding; BMS: Consultancy, Honoraria, Research Funding; AstraZeneca: Honoraria; Astex: Research Funding; GSK: Consultancy, Honoraria; GenMab: Consultancy, Honoraria, Other: data safety board; Riegel: Honoraria; Immunogen: Honoraria; Rigel: Research Funding; Amgen: Consultancy; Astellas: Consultancy, Honoraria; Gilead: Consultancy; Genetech: Honoraria; Servier: Consultancy, Honoraria, Other: meetingsupport, Research Funding; Notable Labs: Honoraria; Foghorn: Research Funding; Abbvie: Consultancy, Honoraria, Research Funding; ImmuneOnc: Research Funding; Schrodinger: Consultancy, Honoraria; Cleave: Research Funding; Jazz: Consultancy, Honoraria; Stemline: Consultancy. Issa: Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: consultancy/ad board fees; AstraZeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: consultancy/ad board fees; Syndax Pharmaceuticals, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: consultancy/ad board fees, Research Funding; NuProbe: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: consultancy/ad board fees, Research Funding; Astex: Research Funding; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: consultancy/ad board fees; Merck: Research Funding; Celgene: Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: consultancy/ad board fees, Research Funding; Kura Oncology: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: consultancy/ad board fees, Research Funding.
See more of: Oral and Poster Abstracts