A study to assess the efficacy of enasidenib and risk-adapted addition of azacitidine in newly diagnosed IDH2-mutant AML Journal Article
| Authors: | Cai, S. F.; Huang, Y.; Lance, J. R.; Mao, H. C.; Dunbar, A. J.; McNulty, S. N.; Druley, T.; Li, Y.; Baer, M. R.; Stock, W.; Kovacsovics, T.; Blum, W. G.; Schiller, G. J.; Olin, R. L.; Foran, J. M.; Litzow, M.; Lin, T.; Patel, P.; Foster, M. C.; Boyiadzis, M.; Collins, R. H.; Chervin, J.; Shoben, A.; Vergilio, J. A.; Heerema, N. A.; Rosenberg, L.; Chen, T. L.; Yocum, A. O.; Druggan, F.; Marcus, S.; Stefanos, M.; Druker, B. J.; Mims, A. S.; Borate, U.; Burd, A.; Byrd, J. C.; Levine, R. L.; Stein, E. M. |
| Article Title: | A study to assess the efficacy of enasidenib and risk-adapted addition of azacitidine in newly diagnosed IDH2-mutant AML |
| 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 ENAmonotherapy 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. © 2024 by The American Society of Hematology. |
| Journal Title: | Blood Advances |
| Volume: | 8 |
| Issue: | 2 |
| ISSN: | 2473-9529 |
| Publisher: | American Society of Hematology |
| Date Published: | 2024-01-23 |
| Start Page: | 429 |
| End Page: | 440 |
| Language: | English |
| DOI: | 10.1182/bloodadvances.2023010563 |
| PUBMED: | 37871309 |
| PROVIDER: | scopus |
| PMCID: | PMC10827405 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PDF -- Corresponding author is MSK author: Eytan Stein -- Source: Scopus |
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