Idhifa (enasidenib) / BMS, Royalty, Servier, Schrodinger - LARVOL DELTA

Outcomes of Frontline Triplet Regimens With a Hypomethylating Agent, Venetoclax, and Isocitrate Dehydrogenase Inhibitor for Intensive Chemotherapy-Ineligible Patients With Isocitrate Dehydrogenase-Mutated AML. (PubMed, J Clin Oncol) - P1/2 | "Given the excellent outcomes of IDH-triplet therapy for newly diagnosed, IC-ineligible IDH-mutant AML, further prospective studies comparing IDH-triplet versus IDH-doublet regimens are warranted."

Journal • Acute Myelogenous Leukemia • Transplantation • IDH1 • IDH2

Isocitrate Dehydrogenase Inhibitors in Acute Myeloid Leukemia. (PubMed, Chem Biodivers) - "Inhibitors of mutated IDH1 and IDH2, vorasidenib, ivosidenib, olutasidenib, and enasidenib, respectively, were recently approved by the FDA for relapsed/refractory AML. In this review, we mainly focus on IDH inhibitors in leukemia therapy, including the discovery, structure optimization, activity of IDH inhibitors, and applications, which provided the reference for the discovery of new anticancer agents."

Journal • Review • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • IDH1 • IDH2

Enasidenib as Maintenance following Allogeneic Hematopoietic Cell Transplantation for IDH2-Mutated Myeloid Malignancies. (PubMed, Blood Adv) - P1 | "Enasidenib is safe, well-tolerated, with preliminary activity as maintenance therapy following HCT, and merits additional study. The study was registered at ClinicalTrials.gov (NCT03515512)."

Journal • Acute Graft versus Host Disease • Acute Myelogenous Leukemia • Chronic Graft versus Host Disease • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Infectious Disease • Leukemia • Myelodysplastic Syndrome • Novel Coronavirus Disease • Oncology • Transplantation • IDH2

Multicenter Pilot Clinical Trial of Enasidenib As Maintenance Therapy after Allogeneic Hematopoietic Cell Transplantation (alloHCT) in Patients with Acute Myeloid Leukemia (AML) Carrying IDH2 Mutations (TCT-ASTCT-CIBMTR 2024) - P1 | "In conclusion, post-HCT maintenance therapy with enasidenib is safe and feasible with highly favorable survival outcomes in mIDH2 AML. Treatment delays and dose reductions were commonly seen; however, most patients completed their 2-years maintenance."

Clinical • Acute Graft versus Host Disease • Acute Myelogenous Leukemia • Anemia • Chronic Graft versus Host Disease • Graft versus Host Disease • Hematological Malignancies • Immunology • Neutropenia • Thrombocytopenia • Transplantation • IDH1 • IDH2

Enasidenib plus venetoclax in patients with IDH2-mutated relapsed or refractory acute myeloid leukaemia or myelodysplastic syndrome (ENAVEN-AML): a multicentre, single-arm, phase 1b/2 trial. (PubMed, Lancet Haematol) - P1/2 | "Enasidenib plus venetoclax is safe, with no unexpected TEAEs or treatment-related deaths, and shows preliminary activity in patients with relapsed or refractory IDH2-mutated AML and MDS."

IO biomarker • Journal • P1/2 data • Acute Myelogenous Leukemia • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Myelodysplastic Syndrome • Neutropenia • Oncology • Pneumonia • Respiratory Diseases • Septic Shock • Thrombocytopenia • ARG1 • IDH2

Overall survival by IDH2 mutant allele (R140 or R172) in patients with late-stage mutant-IDH2 relapsed or refractory acute myeloid leukemia treated with enasidenib or conventional care regimens in the phase 3 IDHENTIFY trial. (ASCO 2022) - P3 | "Pts were preselected to a CCR (azacitidine, intermediate- or low-dose Ara-C, or supportive care), and were then randomized 1:1 to ENA 100 mg/d or CCR in 28d cycles. Mutational burden and co-mutational profiles differed between pts with mIDH2-R140 and mIDH2-R172 R/R AML. ENA improved survival outcomes for pts with IDH2-R172 mutations, with median OS and 1-year survival rate approximately double those in the CCR arm."

Clinical • P3 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • DNMT3A • FLT3 • IDH2 • JAK2 • NPM1 • RUNX1 • SRSF2 • TMB • TP53

Single-cell proteogenomic analysis of clonal evolution in PDX models of AML treated with IDH inhibitors. (PubMed, Blood Neoplasia) - "Using these models, we tracked clonal evolution under selective pressure from IDH inhibitors and combination therapies, identifying an association between WT1 mutations and ivosidenib (IDH1 inhibitor) monotherapy resistance, as well as an antagonism between ivosidenib and enasidenib (IDH2 inhibitor) when tested in IDH1-mutated cells. Our findings demonstrate how single-cell proteogenomic analysis of PDX models can illuminate drug resistance mechanisms and inform therapeutic strategies."

Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • IDH1 • WT1

FLAG-VENETOCLAX-ENASIDENIB SALVAGE FOR 7+3 FAILURE (EBMT 2026) - "The patient underwent standard induction with the "7+3" regimen (Cytarabine/Idarubicin) plus venetoclax...Consequently, a salvage regimen comprising FLAG (Fludarabine, Cytarabine, G-CSF), venetoclax, and the IDH2-inhibitor enasidenib (100 mg daily) was initiated... This case demonstrates that NGS is indispensable in the management of refractory AML-MRC, specifically for identifying targets like IDH2 when standard venetoclax-based induction fails. The addition of enasidenib to FLAG-based salvage provided a crucial bridge to transplant. Furthermore, for patients who have failed intensive induction, NMA conditioning offers a viable, reduced-toxicity platform for allogeneic HSCT, allowing for successful engraftment and survival in a resource-limited setting."

IO biomarker • Acute Myelogenous Leukemia • B Cell Lymphoma • Bone Marrow Transplantation • Hematological Disorders • Leukemia • Lymphoma • Myelodysplastic Syndrome • ASXL1 • RUNX1 • SRSF2

Phase Ib/2 Study of Oral Decitabine/Cedazuridine (ASTX727) and Venetoclax in Combination with the Targeted Mutant IDH1 Inhibitor Ivosidenib or the Targeted Mutant IDH2 Inhibitor Enasidenib in IDH Mutated Acute Myeloid Leukemia (ASH 2022) - "(Table 1) In the R/R cohort, 78% (n=11) patients had received prior treatment with either an HMA (azacitidine or decitabine), BCL2i and/or IDHi, with a median of 2 prior treatments...There were two patients with possible/probable differentiation syndrome which resolved with medical management (dexamethasone and diuresis)...AEs are anticipated and tolerable. Enrollment to this study is ongoing."

Combination therapy • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Febrile Neutropenia • Hematological Malignancies • Hepatology • Mucositis • Myelodysplastic Syndrome • Neutropenia • Transplantation • IDH1

Sequential One-Pot Synthesis of Diversely Functionalized 1,3,5-Triazines via Cyanuric Chloride with Amino Groups and Boronic Acids. (PubMed, ACS Omega) - "By delicately designing the sequence of reagent addition, this operationally simple protocol exhibits broad functional group tolerance across 22 examples (34-69% yield) performed from milligram to subgram quantities and demonstrates future derivatizations. Finally, the synthetic utility is highlighted by the successful synthesis of the FDA-approved anticancer drug Enasidenib."

Journal • Oncology

Multicenter Pilot Clinical Trial of Enasidenib As Maintenance Therapy after Allogeneic Hematopoietic Cell Transplantation in Patients with Acute Myeloid Leukemia (AML) Carrying IDH2 Mutations (ASH 2022) - P1 | "GVHD prophylaxis consisted of post-transplant cyclophosphamide-based (60%; n=9) or tacrolimus-based (40%; n=6) regimens (Tac/Siro= 4 and Tac/MTX= 2). While treatment delays and dose reductions were common, the majority of the study patients remained on the protocol therapy. Droplet digital PCR testing on bone marrow was done to study clearance of IDH2 clones post-HCT and these results will be available by December 2022."

Clinical • Acute Graft versus Host Disease • Acute Myelogenous Leukemia • Anemia • Chronic Graft versus Host Disease • Graft versus Host Disease • Hematological Malignancies • Immunology • Lymphoma • Multiple Myeloma • Neutropenia • Thrombocytopenia • Transplantation • IDH1 • IDH2

A Study of Enasidenib in People With Clonal Cytopenia of Undetermined Significance (clinicaltrials.gov) - P1 | N=4 | Completed | Sponsor: Memorial Sloan Kettering Cancer Center | Active, not recruiting ➔ Completed | Trial completion date: Oct 2026 ➔ Jan 2026 | Trial primary completion date: Oct 2026 ➔ Jan 2026

Trial completion • Trial completion date • Trial primary completion date • Hematological Disorders • IDH2

A Risk-Adapted Study to Assess the Efficacy of Enasidenib and Subsequent Response-Driven Addition of Azacitidine for Newly Diagnosed IDH2-Mutant AML Patients: 3-Year Follow-up (ASH 2022) - P1/2 | "At three-year follow-up, ENAm continues to be a safe and well-tolerated therapy in ND patients ≥ 60 years old with IDH2m AML both alone and with the risk-adapted addition of AZA. CR/CRi rates are high (48%, adjusted 95% CI 30.3-60.5) and remissions are durable (11.1 months, 95% CI 5.6-41.4). The composite CR (cCR) rate of ENAm appears comparable to the cCR rate achieved with ENA + AZA in AG221-AML-005, a phase 2 study comparing ENA + AZA to AZA alone in ND AML."

Clinical • Acute Myelogenous Leukemia • Anemia • Bone Marrow Transplantation • Hematological Disorders • Oncology • Renal Disease • Transplantation • ENAM • IDH2

A PHASE IB/2 TRIAL OF AN ALL-ORAL "TRIPLET" REGIMEN FOR IDH-MUTATED MYELOID MALIGNANCIES: DECITABINE/CEDAZURIDINE AND VENETOCLAX IN COMBINATION WITH IVOSIDENIB/ENASIDENIB (EHA 2025) - P1/2 | "An all-oral triplet regimen of DEC-C+VEN+IVO/ENA demonstrated an impressive CRc rate in both ND and R/R pts with IDH mutant myeloid neoplasms with no new safety signals."

Combination therapy • Acute Myelogenous Leukemia • Hepatology • Infectious Disease • Myelodysplastic Syndrome • IDH1 • IDH2 • TP53

Targeted therapy with the mutant IDH2 inhibitor enasidenib for high-risk IDH2-mutant myelodysplastic syndrome. (PubMed, Blood Adv) - P2 | "Enasidenib is an effective treatment option for mIDH2 MDS, both in combination with azacitidine for treatment naïve high-risk MDS, and as a single agent after prior HMA therapy. This trial is registered at www.clinicaltrials.gov as NCT03383575."

Clinical • Journal • Acute Myelogenous Leukemia • Constipation • Fatigue • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Hepatology • Leukemia • Myelodysplastic Syndrome • Neutropenia • Oncology • UGT1A1

V-FAST Master Trial: Subgroup Analysis of Outcomes with CPX-351 Plus Midostaurin in Adults with Newly Diagnosed Acute Myeloid Leukemia By FLT3 Mutation Type (ASH 2022) - P1b | "V-FAST (Vyxeos – First Phase Assessment with Targeted Agents) is an open-label, multicenter, multi-arm, nonrandomized, phase 1b master trial (NCT04075747) to evaluate the safety and preliminary efficacy of CPX-351 combined with targeted agents (MID, venetoclax, enasidenib)...In conclusion, preliminary results from the V-FAST trial suggest the combination of CPX-351 + MID is feasible with a manageable safety profile and promising remission rates in adults with newly diagnosed, FLT3-mutated AML. Although conclusions are limited by the small numbers of patients in each subgroup, results are generally consistent for patients with FLT3 ITD and TKD mutations."

Clinical • Acute Myelogenous Leukemia • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Leukopenia • Myelodysplastic Syndrome • Neutropenia • Oncology • Thrombocytopenia • Transplantation • FLT3

Phase Ib/2 Study of Oral Decitabine/Cedazuridine (ASTX727) and Venetoclax in Combination with the Targeted Mutant IDH1 Inhibitor Ivosidenib or the Targeted Mutant IDH2 Inhibitor Enasidenib: 2023 Update (ASH 2023) - "AEs were anticipated and tolerable. Enrollment is ongoing."

Combination therapy • Acute Myelogenous Leukemia • Hepatology • Mucositis • CYP3A4 • IDH1 • IDH2

Molecularly Targeted Combination Therapy for Advanced Phase Myeloproliferative Neoplasm: MPN-RC 119 (ASH 2022) - P2 | "Combination treatment with ruxolitinib and enasidenib appear safe with manageable toxicity profile. The majority of grade 3/4 AEs were hematologic as expected in this advanced patient population. Results are encouraging and warrant continued evaluation of this IDH2 mutant defined poor prognostic group."

Combination therapy • Bone Marrow Transplantation • Febrile Neutropenia • Hematological Disorders • Hepatology • Myelofibrosis • Myeloproliferative Neoplasm • Oncology • Transplantation

Multi-institutional retrospective study of IDH2-mutated cholangiocarcinoma. (ASCO-GI 2026) - "Of 33 pts with advanced stage, 1L therapy was gemcitabine/platinum +/- devimistat or durvalumab in 84.9%. Most pts with IDH2 mutation had advanced ds with median survival similar to those with IDH1 mutated advanced cholangiocarcinoma. Off label enasidenib had modest benefit in this rare subset of pts and should be investigated further."

Retrospective data • Biliary Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor • ARID1A • BAP1 • CDKN2A • FGFR2 • IDH1 • IDH2 • KRAS • PBRM1 • TP53

Efficacy of novel agents in the treatment of acute myeloid leukemia and myelodysplastic syndrome: A systematic review and meta-analysis (ASH 2025) - "Newer agents included for AML were Guadectiabine, Magrolimab, Alvocidib, Enasidenib, Flotetuzumab, Vadastuximab, Mitoxantrone, Pevonedistat, Entospletinib, Eprenetapopt, Belinostat, Onvansertib, Panobinostat, Cediranib Maleate, Nilotinib, Emavusertib, and anti-CD45 antibody (DOTA-BC8). The newer agents investigated for MDS included Rigosertib, Imetelstat, Pembrolizumab, Enasidenib, Sabatolimab, Ivosidenib, Elitercept, Pevonedistat, Emavusertib, Atezolizumab, and Olutasidenib...All patients were treated concomitantly with either azacitidine (77%) or decitabine (23%)... This meta-analysis and systematic review demonstrate promising efficacy for novel agents in AML and MDS patients. There is a need for prospective trials with larger patient populations to investigate these agents further."

Retrospective data • Review • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Neutropenia • TP53

Development and Validation of a Simultaneous Quantification Method for 12 Targeted Therapies and 3 Active Metabolites in Human Plasma Using Liquid Chromatography-Tandem Mass Spectrometry: An Application to Therapeutic Drug Monitoring in Patients With Hematological Malignancies. (PubMed, Ther Drug Monit) - "We developed and validated a sensitive liquid chromatography-tandem mass spectrometry method requiring only 50 µL of plasma volume for the quantification of 12 targeted oral anticancer drugs and 3 active metabolites. This multianalyte assay offers strong potential for TDM in patients receiving contemporary anticancer treatments."

Journal • Hematological Disorders • Hematological Malignancies • Immunology • Oncology • Oral Cancer

Financial Toxicity and Quality of Life in Patients Taking Oral Therapy for Hematologic Malignancies (ASH 2023) - "MethodsWe used database query to identify patients at a midwestern, tertiary care, academic medical center who were 18 years or older and were prescribed Enasidenib, Ivosidenib, Venetoclax, Gilteritinib, Midostaurin, Ibrutinib, Acalabrutinib, Imatinib, Nilotinib, Ponatinib, Bosutinib, Duvelisib, or Idelalisib within the past 3 months. Financial stress and hardship were associated with worse satisfaction with QoL and worse experience of SE. Further study should define change in these features over time and interventions to mitigate distress."

Clinical • HEOR • Acute Myelogenous Leukemia • Chronic Lymphocytic Leukemia • CNS Disorders • Depression • Hematological Malignancies • Mood Disorders • Oncology • Oral Cancer • Psychiatry

Beat AML: Study of Biomarker-Based Treatment of Acute Myeloid Leukemia (clinicaltrials.gov) - P1/2 | N=3000 | Recruiting | Sponsor: Beat AML, LLC | N=2000 ➔ 3000 | Trial completion date: Dec 2026 ➔ Dec 2028 | Trial primary completion date: Dec 2026 ➔ Dec 2028

Biomarker • Enrollment change • Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

NCCN has published updates to the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Myelodysplastic Syndromes, Version 2.2026. (NCCN)

NCCN guideline • Myelodysplastic Syndrome

Exploration of Natural Products for Targeting IDH1/2 Mutations in Acute Myeloid Leukemia Through Ligand-Based Pharmacophore Screening, Docking, ADME-T, and Molecular Dynamic Simulation Approaches. (PubMed, Bioinform Biol Insights) - "Docking and MM-GBSA analyses showed strong affinities with IDH1 (-14.2, -84.45 kcal/mol) and IDH2 (-16.8, -60.73 kcal/mol), exceeding those of reference inhibitors GSK321A (-9.6 kcal/mol) and Enasidenib (-8.9 kcal/mol)...This in silico study provides compelling evidence for Ternstroside D (CNP0166496) as a promising dual inhibitor for IDH1 and IDH2 mutations in AML. Furthermore, in vitro and in vivo studies are warranted to validate these findings."

Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • IDH1 • IDH2