A study to assess the efficacy of enasidenib and risk-adapted addition of azacitidine in newly diagnosed IDH2-mutant AML.

Autor:	Cai SF; Division of Hematologic Malignancies, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY., Huang Y; Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, OH., Lance JR; Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, OH., Mao HC; Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, OH., Dunbar AJ; Division of Hematologic Malignancies, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY., McNulty SN; Invitae, San Francisco, CA., Druley T; Invitae, San Francisco, CA., Li Y; Bristol Myers Squibb, New York, NY., Baer MR; University of Maryland Greenebaum Comprehensive Cancer Center, Baltimore, MD., Stock W; Department of Hematology and Oncology, University of Chicago Medical Center, Chicago, IL., Kovacsovics T; Huntsman Cancer Institute, Salt Lake City, UT., Blum WG; Department of Hematology and Medical Oncology, Emory University, Atlanta, GA., Schiller GJ; David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA., Olin RL; Helen Diller Family Comprehensive Cancer Center, San Francisco, CA., Foran JM; Department of Hematology, Mayo Clinic, Jacksonville, FL., Litzow M; Department of Hematology, Mayo Clinic, Rochester, MN., Lin T; Division of Hematologic Malignancies and Cellular Therapeutics, University of Kansas, Kansas City, KS., Patel P; Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX., Foster MC; Lineberger Comprehensive Cancer Center, Chapel Hill, NC., Boyiadzis M; Division of Hematolog/Oncology, Department of Medicine, University of Pittsburgh Cancer Institute, Pittsburgh, PA., Collins RH; Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX., Chervin J; Division of Hematologic Malignancies, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY., Shoben A; Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, OH., Vergilio JA; Foundation Medicine, Inc, Cambridge, MA., Heerema NA; Division of Hematologic Malignancies, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY., Rosenberg L; Leukemia and Lymphoma Society, Rye Brook, NY., Chen TL; Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, OH., Yocum AO; Leukemia and Lymphoma Society, Rye Brook, NY., Druggan F; Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, OH., Marcus S; Leukemia and Lymphoma Society, Rye Brook, NY., Stefanos M; Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, OH., Druker BJ; Knight Cancer Institute, Portland, OR., Mims AS; Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, OH., Borate U; Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, OH., Burd A; Leukemia and Lymphoma Society, Rye Brook, NY., Byrd JC; Department of Internal Medicine, University of Cincinnati, Cincinnati, OH., Levine RL; Division of Hematologic Malignancies, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY., Stein EM; Division of Hematologic Malignancies, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.
Jazyk:	angličtina
Zdroj:	Blood advances [Blood Adv] 2024 Jan 23; Vol. 8 (2), pp. 429-440.
DOI:	10.1182/bloodadvances.2023010563
Abstrakt:	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. (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
Databáze:	MEDLINE
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