Enasidenib, a potent and selective inhibitor of isocitrate dehydrogenase-2 (IDH2), is an antineoplastic agent.1, 9
Enasidenib mesylate is used for the treatment of adults with relapsed or refractory acute myeloid leukemia (AML) with isocitrate dehydrogenase-2 (IDH2) mutation.1, 2, 14 Enasidenib has been designated an orphan drug by FDA for the treatment of this cancer.4 An FDA-approved diagnostic test (e.g., Abbott RealTime® IDH2 assay) is required to confirm the presence of IDH2 mutation (peripheral blood or bone marrow) prior to initiation of therapy.1
Efficacy and safety of enasidenib in the treatment of AML are based principally on the results of an open-label, multicenter, 2-cohort, single-arm study (AG221-C-001) in adults with relapsed or refractory AML with IDH2 mutation as detected by the Abbott RealTi m e® IDH2 mutation test.1, 2, 14 The primary measures of efficacy were CR and CRh, duration of response, and loss of transfusion dependence (red blood cells [RBCs] and/or platelets).1 CR was defined as the presence of less than 5% blasts in bone marrow without evidence of disease and with full recovery of peripheral blood cell counts (platelet count exceeding 100,000/mm3 and absolute neutrophil count [ANC] exceeding 1000/mm3), and CRh was defined as the presence of less than 5% blasts in bone marrow without evidence of disease and with partial recovery of peripheral blood cell counts (platelet count exceeding 50,000/mm3 and ANC exceeding 500/mm3).1 Overall, the median age of patients was 68 years (range: 19-100 years); 77% were Caucasian, 62% were ≥65 years of age, 52% were male, 62% had an Eastern Cooperative Oncology Group (ECOG) performance status of 1, 52% had refractory AML, 49% had intermediate-risk cytogenetics, 27% had poor-risk cytogenetics, 79% were transfusion dependent at baseline, and 13% had previously undergone stem cell transplantation.1 Patients enrolled in this study had received a median of 2 prior antineoplastic chemotherapy regimens.1 IDH2 mutations at codon R140 or R172 were present in 78 or 22% of patients, respectively;1, 5 mutations detected in peripheral blood were reported if bone marrow and peripheral blood mutations were inconsistent.1 In this study, 199 adults received an enasidenib dosage of 100 mg orally once daily.1 Therapy was continued until disease progression or unacceptable toxicity occurred.1 At a median follow-up of 6.6 months, CR or CRh was achieved in 23% of patients with a median response duration of 8.2 months; 19% of patients achieved CR.1 The median time to initial CR or CRh was 1.9 months.1 The median time to best response (CR or CRh) was 3.7 months; the majority (85%) of these patients achieved a best response within 6 months of initiating enasidenib therapy.1 Approximately one-third (34%) of patients who were transfusion dependent at baseline became transfusion independent during any 56-day period during the study.1 The majority (76%) of patients who were transfusion independent at baseline remained transfusion independent during any 56-day period during the study.1
International experts recommend allogeneic hematopoietic stem cell transplantation in the first-line setting for all patients with primary refractory AML who are candidates for intensive chemotherapy.200 Patients with relapsed AML who are candidates for intensive chemotherapy should receive salvage chemotherapy followed by allogeneic hematopoietic stem cell transplantation.200 For patients who are not candidates for intensive chemotherapy, these experts state that such patients may be offered hypomethylating agents or low-dose cytarabine (in combination with venetoclax, if available); gilteritinib (if FLT3 -ITD/ FLT3 -TKD mutation- positive); ivosidenib or enasidenib (if IDH1/2 mutation-positive); melphalan; or best supportive care.200
Enasidenib is administered orally without regard to meals.1 The drug should be taken at approximately the same time each day.1 The tablets should be swallowed whole with a glass of water; they should not be chewed, crushed, or split.1
If a dose is vomited, missed, or not taken at the usual time, administer the dose as soon as possible on the same day, and then return to the normal schedule the following day.1 Do not take 2 doses to make up for a missed dose.1
Store enasidenib tablets in the original container with the desiccant at 20-25ºC (excursions permitted between 15-30ºC).1
Dosage of enasidenib mesylate is expressed in terms of enasidenib.1
For the treatment of relapsed or refractory acute myeloid leukemia (AML) with IDH2 mutation, the recommended adult dosage of enasidenib is 100 mg once daily.1 Therapy should be continued until disease progression or unacceptable toxicity occurs.1 In the principal efficacy study, most patients achieved best response within 6 months of initiating enasidenib; therefore, the manufacturer states that therapy should be continued for at least 6 months to allow time for response.1
In patients who present with leukocytosis (leukocyte counts exceeding 30,000/mm3) in the absence of infection, hydroxyurea therapy should be initiated according to standard practices.1 If leukocytosis persists, temporary interruption of enasidenib therapy may be necessary.1
Dosage Modification for Toxicity
If severe pulmonary symptoms requiring respiratory support (i.e., intubation, assisted respiration) occur and/or renal dysfunction persists for more than 48 hours despite systemic corticosteroid therapy, enasidenib should be withheld until the toxicity improves to grade 2 or less.1
If leukocytosis persists despite hydroxyurea therapy, enasidenib therapy should be withheld until leukocyte counts decrease to less than 30,000/mm3; therapy may then be resumed at the initial dosage (100 mg daily).1
In patients who exhibit increases in serum bilirubin concentrations exceeding 3 times the upper limit of normal (ULN) for 2 weeks or more (in the absence of elevated aminotransferase [ALT/AST] concentrations or other hepatic disorders), enasidenib therapy may be continued at a reduced dosage of 50 mg daily.1 When serum bilirubin concentrations improve to less than 2 times the ULN, the dosage of enasidenib should be re-escalated to 100 mg daily.1
In patients who develop grade 3 or greater tumor lysis syndrome, therapy with enasidenib should be withheld.1 When tumor lysis syndrome improves to grade 2 or less, enasidenib may be resumed at a reduced dosage of 50 mg daily; the dosage of enasidenib may be re-escalated to 100 mg daily when tumor lysis syndrome improves to grade 1 or less.1
If grade 3 or greater tumor lysis syndrome recurs, enasidenib therapy should be discontinued.1
If a grade 3 or greater adverse reaction occurs, therapy with enasidenib should be withheld.1 When the toxicity improves to grade 2 or less, enasidenib may be resumed at a reduced dosage of 50 mg daily; the dosage of enasidenib may be re-escalated to 100 mg daily when the toxicity improves to grade 1 or less.1
If the grade 3 or greater adverse reaction recurs, enasidenib therapy should be discontinued.1
No dosage adjustment is necessary in patients with mild hepatic impairment (total bilirubin concentration not exceeding the ULN with AST concentration exceeding the ULN or total bilirubin concentration 1-1.5 times the ULN with any AST concentration).1, 5
No dosage adjustment is necessary in patients with renal impairment.5
No dosage adjustment is necessary in geriatric patients.1
A boxed warning regarding the risk of differentiation syndrome is included in the prescribing information for enasidenib.1 Differentiation syndrome, which may be life-threatening or fatal, occurred in 14% of patients receiving enasidenib in the principal efficacy study;1, 7 approximately one-half of these patients continued therapy without interruption.7 In a subsequent analysis of the principal efficacy study, the incidence of differentiation syndrome with enasidenib may have been as high as 19%, with 5% of cases resulting in fatality.15, 16 Differentiation syndrome following therapy with an isocitrate dehydrogenase-2 (IDH2) inhibitor, including enasidenib, is associated with rapid proliferation and differentiation of myeloid cells.1, 7 Differentiation syndrome has been characterized by acute respiratory distress (dyspnea and/or hypoxia), hypoxia requiring supplemental oxygen, pulmonary infiltrates, renal or hepatic impairment, multiorgan dysfunction, pyrexia, lymphadenopathy, bone pain, peripheral edema, rapid weight gain, rash, and pleural or pericardial effusions in patients receiving enasidenib.1, 7, 12 Differentiation syndrome has been observed with or without concomitant leukocytosis as early as 1 day or up to 5 months after initiation of enasidenib.1
The risk of developing differentiation syndrome associated with IDH2 inhibitor therapy is increased in patients with bone marrow blast counts exceeding 20% and those who have received fewer prior antileukemic therapies.7, 12 High peripheral blast counts and high serum concentrations of LDH are less predictive of the development of differentiation syndrome associated with IDH2 inhibitor therapy than they are of the development of acute promyelocytic leukemia (APL) differentiation syndrome (also known as retinoic acid-APL [RA-APL] syndrome).7, 12
Early recognition and treatment of differentiation syndrome lessens the likelihood of severe illness and death.16 Manifestations of differentiation syndrome may be clinically indistinguishable from manifestations of disease progression or other acute comorbidities; therefore, differentiation syndrome should be suspected if there is no clear alternate etiology.7 If signs or symptoms suggestive of differentiation syndrome occur, IV or oral corticosteroid therapy (e.g., dexamethasone 10 mg every 12 hours) should be initiated and hemodynamic parameters should be monitored until symptoms improve.1, 7 Because enasidenib has a long half-life, signs or symptoms of differentiation syndrome may recur if systemic corticosteroid therapy is discontinued prematurely;1, 7 therefore, corticosteroid therapy should be continued until symptoms resolve followed by tapering of the corticosteroid dosage.1 If severe pulmonary symptoms requiring respiratory support (i.e., intubation, assisted respiration) occur and/or renal dysfunction persists for more than 48 hours despite corticosteroid therapy, enasidenib should be temporarily interrupted until symptoms improve.1 The manufacturer recommends close monitoring in a hospital setting in patients with pulmonary and/or renal manifestations of differentiation syndrome.1
Other Warnings and Precautions
Fetal/Neonatal Morbidity and Mortality
Enasidenib may cause fetal harm in humans based on animal findings; the drug has been shown to be teratogenic, embryotoxic, and fetotoxic in animals.1 There are no available data regarding the risk of enasidenib use in pregnant patients to date.1 In animal reproduction studies, postimplantation loss, increased rate of resorption, decreased fetal body weight, and skeletal anomalies were observed in rats receiving enasidenib at a maternally toxic dosage (exposure level equivalent to approximately 1.6 times the human exposure at the recommended human dosage).1 The drug also was abortifacient in rabbits receiving enasidenib at exposure levels below the human exposure at the recommended dosage.1
Pregnancy should be avoided during enasidenib therapy.1 Females of reproductive potential and males who are partners of such females should use adequate methods of contraception while receiving the drug and for 2 months after the drug is discontinued.1 Patients using hormonal contraceptives should be advised to use an effective non-hormonal contraceptive method during treatment with enasidenib and for 2 months after the final dose.1
Enasidenib may cause fetal harm if administered to pregnant patients based on animal findings.1
Pregnancy status should be confirmed prior to initiation of enasidenib therapy.1 If enasidenib is used during pregnancy or if the patient or their partner becomes pregnant during therapy, the patient should be informed of the potential fetal hazard.1
It is not known whether enasidenib or its metabolites are distributed into human milk.1 Because of the potential for serious adverse reactions to enasidenib in nursing infants, women should be advised to discontinue nursing during enasidenib therapy.1 Women may begin nursing 2 months after discontinuance of therapy.1 The effects of the drug on nursing infants or on the production of milk are unknown.1
Females and Males of Reproductive Potential
Pregnancy status should be confirmed prior to initiation of enasidenib therapy.1 Females of reproductive potential and males who are partners of such females should use adequate methods of contraception while receiving the drug and for 2 months after the drug is discontinued.1 Patients using hormonal contraceptives should be advised to use an effective non-hormonal contraceptive method during treatment with enasidenib and for 2 months after the final dose.1
Results of toxicity studies in animals suggest that enasidenib may impair female and male fertility.1 In a general toxicology study, decreased corpora lutea, uterine degeneration, and increased ovarian atretic follicles were observed in female animals and seminiferous tubular degeneration, seminal vesicle and prostate atrophy, and hypospermia were observed in male animals receiving enasidenib twice daily for up to 90 days; reversibility of these changes is unknown.1
Safety and efficacy of enasidenib have not been established in pediatric patients.1
In the principal efficacy study, 61% of patients receiving enasidenib were ≥65 years of age and 24% were ≥75 years of age.1 No overall differences in safety and efficacy were observed between these geriatric patients and younger adults.1
In a pharmacokinetic population analysis, age (range of 19-100 years) did not have a substantial effect on the pharmacokinetics of enasidenib.1, 5
In a population pharmacokinetic analysis, mild hepatic impairment (total bilirubin concentration not exceeding the upper limit of normal [ULN] with AST concentration exceeding the ULN or total bilirubin concentration 1-1.5 times the ULN with any AST concentration) did not have a substantial effect on the systemic exposure of enasidenib.1, 5 However, since enasidenib is eliminated principally by hepatic metabolism, hepatic impairment may result in increased exposure to the drug and increased potential for adverse reactions.5
Enasidenib undergoes minimal renal elimination.5
In a population pharmacokinetic analysis, renal impairment (estimated glomerular filtration rate [GFR] of 30 mL/minute or more)5 did not have a substantial effect on the systemic exposure of enasidenib.1, 5
Adverse effects reported in ≥20% of patients receiving enasidenib in clinical studies include nausea, vomiting, diarrhea, elevated bilirubin, and decreased appetite.1
Metabolism of enasidenib to the active AGI-16903 metabolite is mediated by cytochrome P-450 (CYP) isoenzymes 1A2, 2B6, 2C8, 2C9, 2C19, 2D6, and 3A4 and by uridine diphosphate-glucuronosyl transferases (UGT) 1A1, 1A3, 1A4, 1A9, 2B7, and 2B15.1 AGI-16903 is subsequently metabolized by CYP isoenzymes 1A2, 2C19, and 3A4 and by UGT1A1, 1A3, and 1A9.1
In vitro, enasidenib inhibits CYP isoenzymes 1A2, 2B6, 2C8, 2C9, 2C19, 2D6, and 3A4; enasidenib also inhibits UGT1A1.1 In vitro, AGI-16903 inhibits CYP isoenzymes 1A2, 2B6, 2C8, 2C9, 2C19, and 2D6.1 In vitro studies show that enasidenib induces CYP isoenzymes 2B6 and 3A4.1
In vitro studies indicate that enasidenib inhibits P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), organic anion transporter (OAT) 1, organic anion transport protein (OATP) 1B1, OATP1B3, and organic cation transporter (OCT) 2, but does not inhibit multidrug resistance protein 2 (MRP2) or OAT3.1 In vitro, AGI-16903 inhibits BCRP, OAT1, OAT3, OATP1B1, and OCT2, but does not inhibit P-gp, MRP2, or OATP1B3.1 In vitro, AGI-16903 is a substrate of efflux transporters P-gp and BCRP; enasidenib is not a substrate of these transporters.1 Neither enasidenib nor AGI-16903 is a substrate of MRP2, OATP1B1, OATP1B3, OAT1, OAT3, or OCT2.1
Drugs Affecting or Affected by Hepatic Microsomal Enzymes
Substrates of CYP1A2 and CYP2C19
Concomitant use of enasidenib with certain substrates of CYP1A2 and CYP2C19 may increase systemic exposure to the substrate drug and increase the risk of adverse reactions to the drug.1 When a CYP1A2 substrate (caffeine 100 mg) was administered concomitantly with enasidenib, peak plasma concentrations of caffeine were increased by 18%, and systemic exposure to caffeine was increased by 655%.1 When a CYP2C19 substrate (omeprazole 40 mg) was administered concomitantly with enasidenib, peak plasma concentrations of omeprazole were increased by 47%, and systemic exposure to omeprazole increased by 86%.1
Avoid concomitant use with enasidenib unless otherwise recommended in the prescribing information for CYP1A2 or CYP2C19 substrates where minimal concentration changes may lead to serious adverse reactions.1 For caffeine, consider reducing the frequency of caffeine intake in a 24 hour period while taking enasidenib as the drug may increase caffeine-related effects in sensitive individuals.1
Concomitant use of enasidenib with certain substrates of CYP3A may decrease systemic exposure to the substrate drug and reduce the efficacy of the drug.1 When a CYP3A substrate (midazolam 0.3 mg/kg IV) was administered concomitantly with enasidenib, peak plasma concentrations of midazolam were reduced by 23%, and systemic exposure to midazolam was reduced by 43%.1 The decrease in midazolam exposure following oral administration is expected to be even larger than that following IV administration.1
Avoid concomitant use with enasidenib unless otherwise recommended in the prescribing information for CYP3A substrates where minimal concentration changes may lead to reduced efficacy.1 Antifungal agents that are CYP3A substrates should not be administered with enasidenib.1 Concomitant administration of enasidenib with hormonal contraceptives may reduce plasma concentrations of the hormonal contraceptive; patients should consider alternative methods of contraception if receiving enasidenib.1
Substrates of Transport Systems
Substrates of OATP1B1, OATP1B3, and BCRP
Concomitant use of enasidenib with substrates of OATP1B1, OATP1B3, and BCRP may increase systemic exposure to the substrate drug and increase the risk of adverse reactions to the drug.1 When such a substrate drug (rosuvastatin 10 mg) was administered concomitantly with enasidenib, peak plasma concentrations of rosuvastatin were increased by 366%, and systemic exposure to rosuvastatin was increased by 244%.1 Avoid coadministration of enasidenib with OATP1B1, OATP1B3, and BCRP substrates, for which minimal concentration changes may lead to serious toxicities.1 If concomitant use of enasidenib with a OATP1B1, OATP1B3, and BCRP substrate is necessary, the dosage of the substrate drug should be reduced in accordance with the respective prescribing information.1
Concomitant use of enasidenib with substrates of P-gp may increase systemic exposure to the substrate drug and increase the risk of adverse reactions of the drug.1 When a P-gp substrate (digoxin 0.25 mg) was administered concomitantly with enasidenib, peak plasma concentrations of digoxin were increased by 26%, and systemic exposure to digoxin was increased by 20%.1 If concomitant use of enasidenib with a sensitive P-gp substrate is necessary, follow recommendations within the P-gp substrate prescribing information and monitor more frequently for adverse reactions.1
Enasidenib, a potent and selective inhibitor of isocitrate dehydrogenase-2 (IDH2), is an antineoplastic agent.1, 9 Isocitrate dehydrogenases (IDH) are metabolic enzymes in the citric acid cycle responsible for the oxidative decarboxylation of isocitrate to α-ketoglutarate, which is essential for normal cellular processes.5, 6, 12 Approximately 15-20% of acute myeloid leukemia (AML) cases carry IDH2 mutations.2, 8 The most common IDH2 mutation is a point mutation at codon R140Q;6, 8, 9, 10, 13 a less frequently occurring IDH2 mutation is a point mutation at codon R172K.8, 10, 13 IDH2 mutations cause a reduction of α-ketoglutarate to the oncometabolite 2-hydroxyglutarate, which competitively inhibits α-ketoglutarate-dependent dioxygenases resulting in epigenetic dysregulation and subsequent histone and DNA hypermethylation and differentiation arrest of hematopoietic stem cells.2, 5, 10, 11, 12, 13 In vitro studies indicate that enasidenib inhibits IDH2 with R140Q, R172S, or R172K mutation at approximately 40-fold lower concentrations than IDH2 wild-type enzymes.1 Enasidenib has demonstrated decreased 2-hydroxyglutarate levels and induction of myeloid cell differentiation in vitro and in mice bearing tumor xenografts that expressed IDH2 mutation.1 Enasidenib also has demonstrated decreased 2-hydroxyglutarate levels, reduced blast cell counts, and increased percentages of mature myeloid cells in patients with AML that expressed IDH2 mutation.1 In the phase 1/2 study evaluating enasidenib in patients with relapsed or refractory AML, mature granulocytes retained baseline IDH2 mutations and cytogenetic abnormalities in patients who achieved remission, indicating continued differentiation of abnormal myeloblast cells into mature granulocytes.2, 11
Following oral administration of enasidenib, the absolute bioavailability of the drug is 57%.1 Area under the serum concentration-time curve (AUC) of enasidenib is dose proportional over the enasidenib dosage range of 50-450 mg daily.1 Following oral administration of a single dose, median time to peak plasma concentrations of enasidenib is 4 hours.1 Repeated administration of enasidenib resulted in an approximately tenfold mean enasidenib accumulation ratio.1 Steady-state concentrations are reached within 29 days.1 Systemic exposure of enasidenib was increased by 50% when enasidenib was administered with a high-fat meal; however, this effect is not considered clinically important.5 Enasidenib is metabolized to the active AGI-16903 metabolite by cytochrome P-450 (CYP) isoenzymes 1A2, 2B6, 2C8, 2C9, 2C19, 2D6, and 3A4 and by uridine diphosphate-glucuronosyl transferases (UGT) 1A1, 1A3, 1A4, 1A9, 2B7, and 2B15.1 AGI-16903 is subsequently metabolized by CYP isoenzymes 1A2, 2C19, and 3A4 and by UGT1A1, 1A3, and 1A9.1 Enasidenib and AGI-16903 are highly bound (98.5 and 96.6%, respectively) to plasma proteins.1 The terminal half-life of enasidenib is 7.9 days.1 Following administration of a radiolabeled dose of enasidenib, 89% of the radioactivity was recovered in feces (34% of the dose as unchanged drug) and 11% was recovered in urine (0.4% of the dose as unchanged drug).1
The pharmacokinetics of enasidenib do not appear to be affected substantially by age (19-100 years), gender, race, body weight (39-136 kg), or body surface area.1, 5
Additional Information
The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care. For further information on the handling of antineoplastic agents, see the ASHP Guidelines on Handling Hazardous Drugs at [Web].
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Enasidenib mesylate can only be obtained through select specialty pharmacies and distributors.3 Consult manufacturer's website for specific availability information.3
AHFS® Drug Information. © Copyright, 1959-2026, Selected Revisions June 10, 2024. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, MD 20814.
1. Celgene. Idhifa® (enasidenib) tablets prescribing information. Summit, NJ; 2023 Dec.
2. Stein EM, DiNardo CD, Pollyea DA et al. Enasidenib in mutant relapsed or refractory acute myeloid leukemia. Blood . 2017; 130:722-731. [PubMed 28588020]
3. Celgene. Idhifa®: Access and support resources and celgene patient support. From Celgene for Healthcare Professionals website. Accessed 2024 Apr22. [Web]
4. Food and Drug Administration. Search orphan drug designations and approvals. From FDA website. Accessed 2022 Mar 23. [Web]
5. Food and Drug Administration. Center for Drug Evaluation and Research. Application number 209606Orig1s000: Multi-discipline review. From FDA website. [Web]
6. Chen J, Yang J, Sun X et al. Allosteric inhibitor remotely modulates the conformation of the orthestric pockets in mutant IDH2/R140Q. Sci Rep . 2017; 7:16458. [PubMed 29184081]
7. Fathi AT, DiNardo CD, Kline I et al. Differentiation Syndrome Associated With Enasidenib, a Selective Inhibitor of Mutant Isocitrate Dehydrogenase 2: Analysis of a Phase 1/2 Study. JAMA Oncol . 2018; [PubMed 29346478]
8. Stein EM. Molecular Pathways: IDH2 Mutations-Co-opting Cellular Metabolism for Malignant Transformation. Clin Cancer Res . 2016; 22:16-9. [PubMed 26553750]
9. Yen K, Travins J, Wang F et al. AG-221, a First-in-Class Therapy Targeting Acute Myeloid Leukemia Harboring Oncogenic Mutations. Cancer Discov . 2017; 7:478-493. [PubMed 28193778]
10. Perl AE. The role of targeted therapy in the management of patients with AML. Blood Adv . 2017; 1:2281-2294. [PubMed 29296877]
11. Nassereddine S, Lap CJ, Haroun F et al. The role of mutant IDH1 and IDH2 inhibitors in the treatment of acute myeloid leukemia. Ann Hematol . 2017; 96:1983-1991. [PubMed 29090344]
12. Patel SA. Enasidenib-Induced Differentiation Syndrome in IDH2-Mutant Acute Myeloid Leukemia. JAMA Oncol . 2018; [PubMed 29346477]
13. Stein EM. Enasidenib, a targeted inhibitor of mutant IDH2 proteins for treatment of relapsed or refractory acute myeloid leukemia. Future Oncol . 2018; 14:23-40. [PubMed 29243965]
14. Stein EM, DiNardo CD, Fathi AT et al. Molecular remission and response patterns in patients with mutant-IDH2 acute myeloid leukemia treated with enasidenib. Blood . 2019; 133:676-687. [PubMed 30510081]
15. Norsworthy KJ, Mulkey F, Scott EC et al. Differentiation Syndrome with Ivosidenib and Enasidenib Treatment in Patients with Relapsed or Refractory IDH-Mutated AML: A U.S. Food and Drug Administration Systematic Analysis. Clin Cancer Res . 2020; 26:4280-4288. [PubMed 32393603]
16. Food and Drug Administration. FDA warns that symptoms of a serious condition affecting the blood cells are not being recognized with the leukemia medicine Idhifa (enasidenib). From FDA website. Published 2018 November 29. Accessed 2022 March 25 [Web]
200. Heuser M, Ofran Y, Boissel N et al. Acute myeloid leukaemia in adult patients: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol . 2020; 31:697-712. [PubMed 32171751]