{"doi":"10.1002/ajh.26122","title":"Decitabine and venetoclax for <i><scp>IDH1/2</scp>‐</i>mutated acute myeloid leukemia","abstract":"Isocitrate dehydrogenase (IDH) 1/2 mutations occur in approximately 20% of older patients with acute myeloid leukemia (AML). Ivosidenib, an IDH1 inhibitor, is approved for the treatment of relapsed/refractory (R/R) IDH1mut AML and newly diagnosed (ND) patients ineligible for standard therapy, and enasidenib, an IDH2 inhibitor in IDH2mut R/R AML. In ND IDH1mut AML, ivosidenib offers complete remission (CR) plus CR with partial hematologic recovery (CRh) rate of 42% and median overall survival (OS) of 12.6 months, and in the R/R setting, CR/CRh of 30% and median OS of 8.8 months.1 Comparably, enasidenib in ND IDH2mut AML patients showed a CR/CR with incomplete hematologic recovery (CRi) rate of 21% and median OS of 11.3 months, and in R/R patients, a CR/CRi of 26% and median OS of 8.8 months.2 Venetoclax with hypomethylating agent (HMA) is now standard for elderly patients ineligible for intensive therapy. Preclinical studies have shown that IDH1/2mut primary AML cells are highly sensitive to BCL-2 inhibition which was confirmed by clinical studies showing durable responses in IDH1/2mut patients receiving venetoclax monotherapy. In the recently published randomized placebo-controlled trial, venetoclax and azacitidine showed a CR/CRi rate of 75% of patients with ND IDH1/2mutAML with a median OS of 24.5 months.3 Herein, we describe the outcomes of patients with treatment naïve and previously treated IDH1/2mut AML, who were treated on a prospective phase 2 trial of 10-day decitabine with venetoclax (DEC10-VEN, NCT03404193).4 Older patients with ND patients (>60 years) and adult patients >18 years with secondary AML (sAML) from antecedent hematological disorder (AHD), with or without prior therapy for AHD, and R/R AML, with ECOG performance status ≤3 without prior BCL-2 inhibitor exposure were enrolled. In line with our prior report and due to differences in outcomes, we classified treatment-naïve AML as ND AML or sAML without prior therapy for AHD, and the previously treated group as patients with prior treatment for AHD or R/R AML. Patients received 10-day decitabine at 20 mg/m2/day for induction followed by 5-days for consolidation. Venetoclax dose was 400 mg PO daily or equivalent (with azole co-administration). Full protocol of the study have been published previously.4 Reduction in venetoclax duration to <21 days per cycle was allowed to mitigate any myelosuppression. Addition of IDH1/2 inhibitors was allowed. Responses, OS, and relapse-free survival (RFS) were graded per ELN2017 guidelines for AML. Measurable residual disease (MRD) was assessed on bone marrow specimens using multiparametric flow cytometry (FCM) validated to a sensitivity level of 0.01%-0.1%. IDH1/2mut testing was performed using a next-generation sequencing panel with an analytical sensitivity of 5% mutant reads in a background of wild-type reads; or separately using Sanger sequencing during follow-up (variant allele frequency sensitivity 20%). Between January 20, 2018 and March 19, 2020, we treated 10 and 25 patients with IDH1mut and IDH2mut AML, respectively (Table S1). No patients with IDH1mut received concurrent ivosidenib. Among patients with treatment naive IDH1mut AML (n = 7), the median age was 69 years (range, 65-77), and three (43%) patients had adverse risk AML per ELN 2017. ND IDH1mut AML cohort was enriched with DNMT3A (57%), NPM1, SRSF2 (43% each) mutations (Figure 1(F)). The overall response rate (ORR) was 100% (n = 7/7) with MRD negativity by FCM (MRDneg) achieved in 43% patients (n = 3/7) (Figure 1(A)). The 60-day mortality was 0%. After a median follow-up of 23.2 months three patients have relapsed (43%). The 1-year OS was 71% and 1-year RFS was 84% (Figure 1(B) and (C)). Three patients with previously treated IDH1mut AML had a median age of 77 years (range, 75-79) and had received a median of one prior therapy for AHD or AML (range, 1-2). This cohort was enriched with DNMT3A, K/NRAS, NPM1, PHF6, TP53 (33% each) (Figure 1(F)). Only one patie","journal":"American Journal of Hematology","year":2021,"id":172298,"datarank":1.4399856013627244,"base_score":3.258096538021482,"endowment":3.258096538021482,"self_citation_contribution":0.4887144807032224,"citation_network_contribution":0.951271120659502,"self_endowment_contribution":0.4887144807032224,"citer_contribution":0.951271120659502,"corpus_percentile":null,"corpus_rank":null,"citation_count":25,"citer_count":18,"citers_with_citation_signal":17,"citers_with_endowment":17,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9545,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT03404193"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":232836,"name":"Abhishek Maiti","orcid":"0000-0001-9043-538X","position":1,"is_corresponding":false},{"id":109577,"name":"Courtney D. DiNardo","orcid":"0000-0001-9003-0390","position":2,"is_corresponding":false},{"id":109581,"name":"Sanam Loghavi","orcid":"0000-0001-8980-3202","position":3,"is_corresponding":false},{"id":232840,"name":"Naval Daver","orcid":"0000-0001-7103-373X","position":4,"is_corresponding":false},{"id":232841,"name":"Tapan M. Kadia","orcid":"0000-0002-9892-9832","position":5,"is_corresponding":false},{"id":232837,"name":"Caitlin R. Rausch","orcid":"0000-0002-4166-5717","position":6,"is_corresponding":false},{"id":232844,"name":"Yesid Alvarado","orcid":"0000-0002-1652-7937","position":7,"is_corresponding":false},{"id":232843,"name":"Maro Ohanian","orcid":"0000-0002-1689-4470","position":8,"is_corresponding":false},{"id":232853,"name":"Koji Sasaki","orcid":"0000-0002-9140-0610","position":9,"is_corresponding":false},{"id":230993,"name":"Nicholas J. Short","orcid":"0000-0002-2983-2738","position":10,"is_corresponding":false},{"id":108815,"name":"Koichi Takahashi","orcid":"0000-0002-8027-9659","position":11,"is_corresponding":false},{"id":232847,"name":"Musa Yılmaz","orcid":"0000-0002-4498-4895","position":12,"is_corresponding":false},{"id":230403,"name":"Farhad Ravandi","orcid":"0000-0002-7621-377X","position":13,"is_corresponding":false},{"id":109598,"name":"Hagop M. Kantarjian","orcid":"0000-0002-1908-3307","position":14,"is_corresponding":false},{"id":18373,"name":"Marina Konopleva","orcid":"0000-0002-9347-2212","position":15,"is_corresponding":false},{"id":266848,"name":"Sangeetha Venugopal","orcid":"0000-0002-8641-6415","position":0,"is_corresponding":true}],"reference_count":8,"raw_metadata":null,"created_at":"2026-07-18T23:46:37.150824Z","pmid":"33580980","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":[]}