{"doi":"10.1038/s41408-021-00604-2","title":"Efficacy and safety of enasidenib and azacitidine combination in patients with IDH2 mutated acute myeloid leukemia and not eligible for intensive chemotherapy","abstract":"Abstract Preclinically, enasidenib and azacitidine (ENA + AZA) synergistically enhance cell differentiation, and venetoclax (VEN), a small molecule Bcl2 inhibitor (i) is particularly effective in IDH 2 mutated acute myeloid leukemia ( IDH2 mut AML). This open label phase II trial enrolled patients (pts) with documented IDH2 mut AML. All patients received AZA 75 mg/m 2 /d x 7 d/cycle and ENA 100 mg QD continuously. Concomitant Bcl2i and FLT3i were allowed (NCT03683433).Twenty-six pts received ENA + AZA (median 68 years, range, 24–88); 7 newly diagnosed (ND) and 19 relapsed/refractory (R/R). In R/R AML patients, three had received prior ENA and none had received prior VEN. The composite complete remission rate (CRc) [complete remission (CR) or complete remission with incomplete hematologic recovery (CRi)] was 100% in ND AML, and 58% in R/R AML. Median OS was not reached in ND AML with median follow-up of 13.1 months (mo); Pts treated in first relapse had improved OS than those with ≥2 relapse (median OS not reached vs 5.2 mo; HR 0.24, 95% CI 0.07–0.79, p = 0.04). Two patients received ENA + AZA with a concomitant FLT3i, one responding ND AML patient and one nonresponding R/R AML patient. Seven R/R AML pts received ENA + AZA + VEN triplet, and with median follow up of 11.2 mo, median OS was not reached and 6-mo OS was 70%. The most frequent treatment-emergent adverse events include febrile neutropenia (23%). Adverse events of special interest included all-grade IDH differentiation syndrome (8%) and indirect hyperbilirubinemia (35%). ENA + AZA was a well-tolerated, and effective therapy for elderly pts with IDH2 mut ND AML as well as pts with R/R AML. The addition of VEN to ENA + AZA appears to improve outcomes in R/R IDH2 mut AML. Clinical trial registration information: https://clinicaltrials.gov/.NCT03683433","journal":"Blood Cancer Journal","year":2022,"id":234551,"datarank":2.4623367984258353,"base_score":4.564348191467836,"endowment":4.564348191467836,"self_citation_contribution":0.6846522287201755,"citation_network_contribution":1.77768456970566,"self_endowment_contribution":0.6846522287201755,"citer_contribution":1.77768456970566,"corpus_percentile":null,"corpus_rank":null,"citation_count":95,"citer_count":77,"citers_with_citation_signal":62,"citers_with_endowment":62,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.944,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT03683433"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":108815,"name":"Koichi Takahashi","orcid":"0000-0002-8027-9659","position":1,"is_corresponding":false},{"id":232840,"name":"Naval Daver","orcid":"0000-0001-7103-373X","position":2,"is_corresponding":false},{"id":232836,"name":"Abhishek Maiti","orcid":"0000-0001-9043-538X","position":3,"is_corresponding":false},{"id":232842,"name":"Gautam Borthakur","orcid":"0000-0001-7679-6453","position":4,"is_corresponding":false},{"id":109581,"name":"Sanam Loghavi","orcid":"0000-0001-8980-3202","position":5,"is_corresponding":false},{"id":230993,"name":"Nicholas J. 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Kadia","orcid":"0000-0002-9892-9832","position":13,"is_corresponding":false},{"id":230405,"name":"Michael Andreeff","orcid":"0000-0002-1144-1958","position":14,"is_corresponding":false},{"id":230403,"name":"Farhad Ravandi","orcid":"0000-0002-7621-377X","position":15,"is_corresponding":false},{"id":18373,"name":"Marina Konopleva","orcid":"0000-0002-9347-2212","position":16,"is_corresponding":false},{"id":109598,"name":"Hagop M. Kantarjian","orcid":"0000-0002-1908-3307","position":17,"is_corresponding":false},{"id":109577,"name":"Courtney D. DiNardo","orcid":"0000-0001-9003-0390","position":18,"is_corresponding":false},{"id":266848,"name":"Sangeetha Venugopal","orcid":"0000-0002-8641-6415","position":0,"is_corresponding":true}],"reference_count":30,"raw_metadata":null,"created_at":"2026-07-19T00:21:42.662304Z","pmid":"35078972","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}