Citations 2
Beat-AML 2024 ELN–refined risk stratification for older adults with newly diagnosed AML given lower-intensity therapy
Hoff, Fieke W. , Blum, William , Huang, Ying , Welkie, Rina Li , Swords, Ronan , Traer, Elie , Stein, Eytan M. , Lin, Tara L. , Patel, Prapti A. , Collins, Robert H. , Baer, Maria R. , Arellano, Martha , Odenike, Olatoyosi , Redner, Robert L. , Kovacsovics, Tibor , Deininger, Michael W. , Olin, Rebecca L. , Foran, James M. , Schiller, Gary J. , Curran, Emily , Koenig, Kristin L , Heerema, Nyla A. , Chen, Timothy L. , Martycz, Molly , Stefanos, Mona , Marcus, Sonja G., Rosenberg, Leonard, Burd, Amy , Yocum, Ashley O. , Borate, Uma , Byrd, John C. , Madanat, Yazan F. , Huang, Ying , Byrd, John C. , Duong, Vu H , Deininger, Michael , Zeidner, Joshua F , Smith, Catherine C , Koenig, Kristin L , Druker, Brian J , Mims, Alice S , Madanat, Yazan , Traer, Elie , Lin, Tara L , Byrd, John C , Archer, Kellie J. , Duong, Vu H. , Stock, Wendy , Zeidner, Joshua F. , Smith, Catherine C. , Marcus, Sonja G., Levine, Ross L.
Blood Advances | August 7, 2024 | Volume: 8 | Issue: 20 | Pages: 5297-5305
10.1182/bloodadvances.2024013685
Abstract Although the 2022 European LeukemiaNet (ELN) acute myeloid leukemia (AML) risk classification reliably predicts outcomes in younger patients treated with intensive chemotherapy, it is unclear whether it applies to adults ≥60 years treated with lower-intensity treatment (LIT). We aimed to test the prognostic impact of ELN risk in patients with newly diagnosed (ND) AML aged ≥60 years given LIT and to further refine risk stratification for these patients. A total of 595 patients were included: 11% had favorable-, 11% intermediate-, and 78% had adverse-risk AML. ELN risk was prognostic for overall survival (OS) (P < .001) but did not stratify favorable- from intermediate-risk (P = .71). Within adverse-risk AML, the impact of additional molecular abnormalities was further evaluated. Multivariable analysis was performed on a training set (n = 316) and identified IDH2 mutation as an independent favorable prognostic factor, and KRAS, MLL2, and TP53 mutations as unfavorable (P < .05). A “mutation score” was calculated for each combination of these mutations, assigning adverse-risk patients to 2 risk groups: −1 to 0 points (“Beat-AML intermediate”) vs 1+ points (“Beat-AML adverse”). In the final refined risk classification, ELN favorable- and intermediate-risk were combined into a newly defined “Beat-AML favorable-risk” group, in addition to mutation scoring within the ELN adverse-risk group. This approach redefines risk for older patients with ND AML and proposes refined Beat-AML risk groups with improved discrimination for OS (2-year OS, 48% vs 33% vs 11%, respectively; P < .001), providing patients and providers additional information for treatment decision-making.
A study to assess the efficacy of enasidenib and risk-adapted addition of azacitidine in newly diagnosed IDH2 -mutant AML
Huang, Ying , Lance, Jennie Rachel, Mao, Hsiaoyin, Dunbar, Andrew , McNulty, Samantha N. , Baer, Maria R. , Kovacsovics, Tibor , Blum, William , Schiller, Gary J. , Olin, Rebecca L. , Foran, James M. , Litzow, Mark R. , Patel, Prapti A. , Boyiadzis, Michael , Collins, Robert H. , Chervin, Jordan , Vergilio, Jo‐Anne, Heerema, Nyla A. , Rosenberg, Leonard, Chen, Timothy L. , Yocum, Ashley O. , Druggan, Franchesca , Marcus, Sonja, Stefanos, Mona , Borate, Uma , Burd, Amy , Byrd, John C. , Stein, Eytan M. , Huang, Ying , Cai, Sheng F , Litzow, Mark R. , Lin, Tara L , Druker, Brian J , Mims, Alice S , Byrd, John C , Druley, Todd E. , Li, Yan , Stock, Wendy , Lin, Tara L. , Foster, Matthew C , Shoben, Abigail B. , Levine, Ross L.
Blood Advances | October 23, 2023 | Volume: 8 | Issue: 2 | Pages: 429-440
10.1182/bloodadvances.2023010563
Abstract Enasidenib (ENA) is an inhibitor of isocitrate dehydrogenase 2 (IDH2) approved for the treatment of patients with IDH2-mutant relapsed/refractory acute myeloid leukemia (AML). In this phase 2/1b Beat AML substudy, we applied a risk-adapted approach to assess the efficacy of ENA monotherapy for patients aged ≥60 years with newly diagnosed IDH2-mutant AML in whom genomic profiling demonstrated that mutant IDH2 was in the dominant leukemic clone. Patients for whom ENA monotherapy did not induce a complete remission (CR) or CR with incomplete blood count recovery (CRi) enrolled in a phase 1b cohort with the addition of azacitidine. The phase 2 portion assessing the overall response to ENA alone demonstrated efficacy, with a composite complete response (cCR) rate (CR/CRi) of 46% in 60 evaluable patients. Seventeen patients subsequently transitioned to phase 1b combination therapy, with a cCR rate of 41% and 1 dose-limiting toxicity. Correlative studies highlight mechanisms of clonal elimination with differentiation therapy as well as therapeutic resistance. This study demonstrates both efficacy of ENA monotherapy in the upfront setting and feasibility and applicability of a risk-adapted approach to the upfront treatment of IDH2-mutant AML. This trial is registered at www.clinicaltrials.gov as #NCT03013998.