Missing content? – Request curation!
Request curation for specific Genes, Variants, or PubMed publications.
Have questions, comments, or suggestions? - Let us know!
Email us at : ckbsupport@jax.org
| Gene Symbol | IDH2 | ||||||||||
| Synonyms | D2HGA2 | ICD-M | IDH | IDH-2 | IDHM | IDP | IDPM | mNADP-IDH | ||||||||||
| Gene Description | IDH2, isocitrate dehydrogenase (NADP(+)) 2, is an enzyme that catalyzes the conversion of isocitrate to alpha-ketoglutarate (alpha-KG), and is involved in the tricarboxylic acid cycle (PMID: 28711227, PMID: 28980701). Mutations in IDH2 are associated with aberrant conversion of alpha-KG to 2-HG, which is an oncogenic metabolite, and are recurrent in acute myeloid leukemia and subtypes of glioma (PMID: 27621679, PMID: 19228619, PMID: 23999441). | ||||||||||
|
|||||||||||
| Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|
| IDH2 wild-type | high grade glioma | not applicable | N/A | Guideline | Risk Factor | IDH2 wild-type is associated with increased risk of aggressive disease in patients with grade II or III infiltrative gliomas (NCCN.org). | detail... |
| IDH2 R172K | glioblastoma | predicted - sensitive | Enasidenib | Preclinical - Biochemical | Actionable | In a preclinical study, Enasidenib (AG-221) decreased 2-hydroxyglutarate (2HG) levels in a glioblastoma cell line expressing IDH2 R172K in culture (PMID: 28193778). | 28193778 |
| IDH2 R172K | acute myeloid leukemia | sensitive | Enasidenib | FDA approved - On Companion Diagnostic | Actionable | In a Phase I/II trial that supported FDA approval, Idhifa (enasidenib) treatment resulted in an overall response rate of 40.3% (71/176) with a median response duration of 5.8 months, complete remission in 19.3% (34/176), and stable disease in 48.3% (85/176) of acute myeloid leukemia patients harboring IDH2 mutations (PMID: 28588020; NCT01915498) and IDH2 R172K is on the companion diagnostic. | detail... detail... 28588020 |
| IDH2 R172K | acute myeloid leukemia | sensitive | Enasidenib | Preclinical - Patient cell culture | Actionable | In a preclinical study, Enasidenib (AG-221) decreased 2-hydroxyglutarate (2HG) levels and induced differentiation of leukemic blasts from acute myeloid leukemia (AML) patients harboring IDH2 R172K in culture (PMID: 28193778). | 28193778 |
| IDH2 R172K | colorectal cancer | predicted - sensitive | Enasidenib | Preclinical - Biochemical | Actionable | In a preclinical study, Enasidenib (AG-221) decreased 2-hydroxyglutarate (2HG) levels in a colorectal carcinoma cell line expressing IDH2 R172K in culture (PMID: 28193778). | 28193778 |
| IDH2 R172K | Advanced Solid Tumor | predicted - sensitive | HMPL-306 | Preclinical - Biochemical | Actionable | In a preclinical study, HMPL-306 inhibited the enzymatic activity of IDH2 R172K in a fluorescence-based assay (Cancer Res (2023) 83 (7_Supplement): 543). | detail... |
| IDH2 R172K | hematologic cancer | predicted - sensitive | SH1573 | Preclinical - Biochemical | Actionable | In a preclinical study, SH1573 inhibited the activity of IDH2 R172K in an in vitro assay (PMID: 34221866). | 34221866 |
| IDH2 R172K | acute myeloid leukemia | predicted - sensitive | TQB3455 | Case Reports/Case Series | Actionable | In a Phase I trial, TQB3455 treatment was well tolerated in patients with acute myeloid leukemia harboring IDH2 mutations, and resulted in an objective response rate (ORR) of 40.63% (13/32, 12 complete remission (CR) or CR with incomplete hematological recovery, 1 partial remission), with an ORR of 66.67%, and a CR rate of 41.67% in patients harboring IDH2 R172K (n=14) (Blood (2022) 140 (Supplement 1): 9082-9083). | detail... |
| IDH2 R172K | high grade glioma | sensitive | TQ05310 | Preclinical - Cell culture | Actionable | In a preclinical study, TQ05310 treatment decreased 2-HG levels and increased differentiation in a glioma cell line expressing IDH2 R172K in culture (PMID: 31361380). | 31361380 |
| IDH2 R172K | acute myeloid leukemia | sensitive | TQ05310 | Preclinical - Cell culture | Actionable | In a preclinical study, TQ05310 treatment decreased 2-HG levels and increased differentiation in an acute myeloid leukemia cell line expressing IDH2 R172K in culture (PMID: 31361380). | 31361380 |
| IDH1 R132C IDH2 R172K | intrahepatic cholangiocarcinoma | predicted - resistant | Ivosidenib | Case Reports/Case Series | Actionable | In a clinical case study, IDH2 R172K was identified upon progression in a patient with metastatic intrahepatic cholangiocarcinoma harboring IDH1 R132C, along with PIK3CA E545K, who previously responded to Tibsovo (ivosidenib) (PMID: 36056177). | 36056177 |
| IDH2 R140Q | acute myeloid leukemia | sensitive | AGI-6780 | Preclinical | Actionable | In a preclinical study, treatment with AGI-6780 resulted in the differentiation of erythroleukemia and AML cell lines expressing IDH2 R140Q (PMID: 23558173). | 23558173 |
| IDH2 R140Q | myelodysplastic syndrome | not applicable | N/A | Guideline | Prognostic | IDH2 R140Q is associated with a poor prognosis in patients with myelodysplastic syndrome (NCCN.org). | detail... |
| IDH2 R140Q | glioblastoma | predicted - sensitive | Enasidenib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Enasidenib (AG-221) decreased 2-hydroxyglutarate (2HG) levels in a glioblastoma cell line expressing IDH2 R140Q in culture and in xenograft models (PMID: 28193778). | 28193778 |
| IDH2 R140Q | acute myeloid leukemia | sensitive | Enasidenib | FDA approved - On Companion Diagnostic | Actionable | In a Phase I/II trial that supported FDA approval, Idhifa (enasidenib) treatment resulted in an overall response rate of 40.3% (71/176) with a median response duration of 5.8 months, complete remission in 19.3% (34/176), and stable disease in 48.3% (85/176) of acute myeloid leukemia patients harboring IDH2 mutations (PMID: 28588020; NCT01915498) and IDH2 R140Q is on the companion diagnostic. | detail... detail... 28588020 |
| IDH2 R140Q | acute myeloid leukemia | sensitive | Enasidenib | Preclinical - Pdx & cell culture | Actionable | In a preclinical study, Enasidenib (AG-221) treatment reduced 2-hydroxyglutarate (2HG) levels and induced differentiation of leukemic blasts from acute myeloid leukemia (AML) patients harboring IDH2 R140Q in culture, and decreased 2HG levels and blast percentage and improved survival relative to Cytosar-U (cytarabine) treatment in IDH2 R140Q-mutant primary AML xenograft models (PMID: 28193778). | 28193778 |
| IDH2 R140Q | high grade glioma | predicted - sensitive | Vorasidenib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, AG-881 treatment decreased tumor 2HG levels in a glioma cell line xenograft model harboring IDH2 R140Q (Mol Cancer Ther Jan 1 2018 (17) (1 Supp) B126). | detail... |
| IDH2 R140Q | Advanced Solid Tumor | predicted - sensitive | HMPL-306 | Preclinical - Biochemical | Actionable | In a preclinical study, HMPL-306 inhibited the enzymatic activity of IDH2 R140Q in a fluorescence-based assay (Cancer Res (2023) 83 (7_Supplement): 543). | detail... |
| IDH2 R140Q | leukemia | sensitive | TETi76 | Preclinical - Cell culture | Actionable | In a preclinical study, TETi76 treatment decreased viability of a leukemia cell line expressing IDH2 R140Q in culture (PMID: 33681816). | 33681816 |
| IDH2 R140Q | hematologic cancer | predicted - sensitive | SH1573 | Preclinical - Cell culture | Actionable | In a preclinical study, SH1573 treatment decreased 2-HG levels and increased differentiation of a tumor cell line expressing IDH2 R140Q in culture (PMID: 34221866). | 34221866 |
| IDH2 R140Q | high grade glioma | sensitive | TQ05310 | Preclinical - Cell culture | Actionable | In a preclinical study, TQ05310 treatment decreased 2-HG levels and increased differentiation in a glioma cell line expressing IDH2 R140Q in culture (PMID: 31361380). | 31361380 |
| IDH2 R140Q | acute myeloid leukemia | sensitive | TQ05310 | Preclinical - Cell culture | Actionable | In a preclinical study, TQ05310 treatment decreased 2-HG levels and increased differentiation in an acute myeloid leukemia cell line expressing IDH2 R140Q in culture (PMID: 31361380). | 31361380 |
| IDH2 R140Q IDH2 Q316E | leukemia | predicted - resistant | Enasidenib | Preclinical - Biochemical | Actionable | In a preclinical study, Idhifa (enasidenib) did not inhibit Idh2 activity and R-2HG production in a leukemia cell line expressing IDH2 R140Q and Q316E in culture (PMID: 36222845). | 36222845 |
| IDH2 R140Q IDH2 Q316E | acute myeloid leukemia | resistant | Enasidenib | Case Reports/Case Series | Actionable | In a clinical study, IDH2 Q316E was identified as an acquired mutation in trans with the original IDH2 R140Q in a patient with acute myeloid leukemia (AML), who developed resistance to Idhifa (enasidenib) after initial response, and coexpression of IDH2 Q316E in trans or in cis with IDH2 R140Q conferred resistance to Idhifa (enasidenib) in culture and in animal models of AML, supporting a mechanism of variants cooperating to confer resistance (PMID: 29950729). | 29950729 |
| IDH2 R140Q IDH2 I319M | leukemia | predicted - resistant | Enasidenib | Preclinical - Biochemical | Actionable | In a preclinical study, Idhifa (enasidenib) did not inhibit Idh2 activity and R-2HG production in a leukemia cell line expressing IDH2 R140Q and I319M in culture (PMID: 36222845). | 36222845 |
| IDH2 R140Q IDH2 I319M | acute myeloid leukemia | resistant | Enasidenib | Case Reports/Case Series | Actionable | In a clinical case study, IDH2 I319M was identified as an acquired mutation in a patient with acute myeloid leukemia harboring IDH2 R140Q upon progression on Idhifa (enasidenib) (PMID: 36222845). | 36222845 |
| IDH2 R140Q IDH2 I319M | acute myeloid leukemia | resistant | Enasidenib | Case Reports/Case Series | Actionable | In a clinical study, IDH2 I319M was identified as an acquired mutation in trans with the original IDH2 R140Q in a patient with acute myeloid leukemia (AML), who developed resistance to Idhifa (enasidenib) after initial response, and coexpression of IDH2 I319M in trans or in cis with IDH2 R140Q conferred resistance to Idhifa (enasidenib) in culture, supporting a mechanism of variants cooperating to confer resistance (PMID: 29950729). | 29950729 |
| FLT3 exon 14 ins IDH2 R140Q | acute myeloid leukemia | predicted - sensitive | Crenolanib | Preclinical - Cell culture | Actionable | In a preclinical study, high dosage Crenolanib (CP-868596) treatment resulted in reduced viability of cells isolated from a transgenic mouse model of acute myeloid leukemia harboring a FLT3-ITD mutation and IDH2 R140Q in culture (PMID: 33268594). | 33268594 |
| FLT3 exon 14 ins IDH2 R140Q | acute myeloid leukemia | predicted - resistant | Midostaurin | Preclinical | Actionable | In a preclinical study, Rydapt (midostaurin) failed to inhibit growth of cells isolated from a transgenic mouse model of acute myeloid leukemia harboring a FLT3-ITD mutation and IDH2 R140Q in culture (PMID: 33268594). | 33268594 |
| FLT3 exon 14 ins IDH2 R140Q | acute myeloid leukemia | predicted - resistant | Quizartinib | Preclinical | Actionable | In a preclinical study, Vanflyta (quizartinib) failed to inhibit growth of cells isolated from a transgenic mouse model of acute myeloid leukemia harboring a FLT3-ITD mutation and IDH2 R140Q in culture (PMID: 33268594). | 33268594 |
| FLT3 exon 14 ins IDH2 R140Q | acute myeloid leukemia | predicted - resistant | Sorafenib | Preclinical | Actionable | In a preclinical study, Nexavar (sorafenib) failed to inhibit growth of cells isolated from a transgenic mouse model of acute myeloid leukemia harboring a FLT3-ITD mutation and IDH2 R140Q in culture (PMID: 33268594). | 33268594 |
| FLT3 exon 14 ins IDH2 R140Q | acute myeloid leukemia | predicted - sensitive | Gilteritinib | Preclinical - Cell culture | Actionable | In a preclinical study, high dosage Xospata (gilteritinib) treatment resulted in reduced viability and colony formation of cells isolated from a transgenic mouse model of acute myeloid leukemia harboring a FLT3-ITD mutation and IDH2 R140Q in culture (PMID: 33268594). | 33268594 |
| FLT3 exon 14 ins IDH2 R140Q | acute myeloid leukemia | predicted - sensitive | Enasidenib + Quizartinib | Preclinical | Actionable | In a preclinical study, the combination of Enasidenib (AG-221) and Vanflyta (quizartinib) stimulated leukemic cell differentiation and reduced leukemic cell self-renewal in an acute myeloid leukemia mouse model simultaneously expressing IDH2 R140Q and a FLT3-ITD mutation (Blood Dec 2014, 124 (21) 437). | detail... |
| FLT3 exon 14 ins IDH2 R140Q | acute myeloid leukemia | predicted - sensitive | Dubermatinib | Preclinical | Actionable | In a preclinical study, Dubermatinib (TP-0903) treatment inhibited growth and colony formation of cells isolated from a transgenic mouse model of acute myeloid leukemia harboring a FLT3-ITD mutation and IDH2 R140Q in culture, and increased survival in mouse models (PMID: 33268594). | 33268594 |
| IDH1 R132C IDH1 D279N IDH2 R140Q | acute myeloid leukemia | predicted - resistant | Ivosidenib | Case Reports/Case Series | Actionable | In a Phase I trial, IDH1 D279N and IDH2 R140Q were identified at progression in a patient with acute myeloid leukemia harboring IDH1 R132C who previously responded to Tibsovo (ivosidenib) treatment (PMID: 32380538; NCT02074839). | 32380538 |
| IDH1 R119P IDH1 R132L IDH2 R140Q | acute myeloid leukemia | predicted - resistant | Ivosidenib | Case Reports/Case Series | Actionable | In a Phase I trial, IDH1 R119P and IDH2 R140Q were identified at progression in a patient with acute myeloid leukemia harboring IDH1 R132L who previously responded to Tibsovo (ivosidenib) treatment (PMID: 32380538; NCT02074839). | 32380538 |
| IDH2 R140Q IDH2 H348Q | leukemia | predicted - resistant | Enasidenib | Preclinical - Biochemical | Actionable | In a preclinical study, Idhifa (enasidenib) did not inhibit Idh2 activity and R-2HG production in a leukemia cell line expressing IDH2 R140Q and H348Q in culture (PMID: 36222845). | 36222845 |
| IDH1 R132L IDH2 R140Q | acute myeloid leukemia | predicted - resistant | Ivosidenib | Case Reports/Case Series | Actionable | In a Phase I trial, IDH2 R140Q was identified at progression in a patient with acute myeloid leukemia harboring IDH1 R132L who previously had a response of stable disease with Tibsovo (ivosidenib) treatment (PMID: 32380538; NCT02074839). | 32380538 |
| IDH1 R132C IDH2 R140Q | acute myeloid leukemia | predicted - resistant | Ivosidenib | Case Reports/Case Series | Actionable | In a Phase I trial, IDH2 R140Q was identified at progression in 5 patients with acute myeloid leukemia harboring IDH1 R132C who previously responded to Tibsovo (ivosidenib) treatment (PMID: 32380538; NCT02074839). | 32380538 |
| IDH1 R132H IDH2 R140Q | acute myeloid leukemia | predicted - resistant | Ivosidenib | Case Reports/Case Series | Actionable | In a Phase I trial, IDH2 R140Q was identified at progression in 4 patients with acute myeloid leukemia harboring IDH1 R132H who previously responded to Tibsovo (ivosidenib) treatment (PMID: 32380538; NCT02074839). | 32380538 |
| IDH2 R140Q IDH2 E343V | leukemia | resistant | Enasidenib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, a leukemia cell line expressing IDH2 R140Q and E343V was resistant to Idhifa (enasidenib) in culture and did not reduce tumor burden in a cell line xenograft model (PMID: 36222845). | 36222845 |
| IDH2 R140Q IDH2 E343V | acute myeloid leukemia | predicted - resistant | Enasidenib | Case Reports/Case Series | Actionable | In a clinical case study, IDH2 E343V was identified as an acquired mutation in a patient with acute myeloid leukemia harboring IDH2 R140Q upon progression on Idhifa (enasidenib) (PMID: 36222845). | 36222845 |
| IDH2 R140Q IDH2 E343V | leukemia | predicted - resistant | Vorasidenib | Preclinical - Biochemical | Actionable | In a preclinical study, Vorasidenib (AG-881) did not inhibit R-2HG production in a leukemia cell line expressing IDH2 R140Q and E343V in culture (PMID: 36222845). | 36222845 |
| IDH2 R140Q IDH2 A347T | leukemia | resistant | Enasidenib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, a leukemia cell line expressing IDH2 R140Q and A347T was resistant to Idhifa (enasidenib) in culture and did not reduce tumor burden in a cell line xenograft model (PMID: 36222845). | 36222845 |
| IDH2 R140Q IDH2 A347T | acute myeloid leukemia | predicted - resistant | Enasidenib | Case Reports/Case Series | Actionable | In a clinical case study, IDH2 A347T was identified as an acquired mutation in a patient with acute myeloid leukemia harboring IDH2 R140Q upon progression on Idhifa (enasidenib) (PMID: 36222845). | 36222845 |
| IDH2 R140Q IDH2 A347T | leukemia | predicted - resistant | Vorasidenib | Preclinical - Biochemical | Actionable | In a preclinical study, Vorasidenib (AG-881) did not inhibit R-2HG production in a leukemia cell line expressing IDH2 R140Q and A347T in culture (PMID: 36222845). | 36222845 |
| IDH2 N136S IDH2 R140Q | leukemia | predicted - resistant | Enasidenib | Preclinical - Biochemical | Actionable | In a preclinical study, Idhifa (enasidenib) did not inhibit Idh2 activity and R-2HG production in a leukemia cell line expressing IDH2 R140Q and N136S in culture (PMID: 36222845). | 36222845 |
| IDH2 R140Q IDH2 E345G | leukemia | predicted - resistant | Enasidenib | Preclinical - Biochemical | Actionable | In a preclinical study, Idhifa (enasidenib) did not inhibit Idh2 activity and R-2HG production in a leukemia cell line expressing IDH2 R140Q and E345G in culture (PMID: 36222845). | 36222845 |
| IDH2 R140Q IDH2 V351I | leukemia | predicted - resistant | Enasidenib | Preclinical - Biochemical | Actionable | In a preclinical study, Idhifa (enasidenib) did not inhibit Idh2 activity and R-2HG production in a leukemia cell line expressing IDH2 R140Q and V351I in culture (PMID: 36222845). | 36222845 |
| IDH2 R140Q IDH2 V351I | acute myeloid leukemia | predicted - resistant | Enasidenib | Case Reports/Case Series | Actionable | In a clinical case study, IDH2 V351I was identified as an acquired mutation in a patient with acute myeloid leukemia harboring IDH2 R140Q upon progression on Idhifa (enasidenib) (PMID: 36222845). | 36222845 |
| IDH2 R140Q IDH2 T352A | leukemia | predicted - resistant | Enasidenib | Preclinical - Biochemical | Actionable | In a preclinical study, Idhifa (enasidenib) did not inhibit Idh2 activity and R-2HG production in a leukemia cell line expressing IDH2 R140Q and T352A in culture (PMID: 36222845). | 36222845 |
| IDH2 R140Q IDH2 R353H | leukemia | predicted - resistant | Enasidenib | Preclinical - Biochemical | Actionable | In a preclinical study, Idhifa (enasidenib) did not inhibit Idh2 activity and R-2HG production in a leukemia cell line expressing IDH2 R140Q and R353H in culture (PMID: 36222845). | 36222845 |
| IDH2 R140Q IDH2 L449V | leukemia | predicted - sensitive | Enasidenib | Preclinical - Biochemical | Actionable | In a preclinical study, Idhifa (enasidenib) inhibited enzymatic activity and R-2HG production in a leukemia cell line expressing IDH2 R140Q and L449V in culture (PMID: 36222845). | 36222845 |
| IDH2 R140Q IDH2 G450S | leukemia | predicted - sensitive | Enasidenib | Preclinical - Biochemical | Actionable | In a preclinical study, Idhifa (enasidenib) inhibited enzymatic activity and R-2HG production in a leukemia cell line expressing IDH2 R140Q and G450S in culture (PMID: 36222845). | 36222845 |
| EML4 - ALK IDH2 R140Q | lung adenocarcinoma | predicted - resistant | Alectinib | Case Reports/Case Series | Actionable | In a clinical case study, IDH2 R140Q was identified at progression on Alecensa (alectinib) in a patient with non-small cell lung cancer harboring EML4-ALK (PMID: 34058070). | 34058070 |
| IDH2 R172G | acute myeloid leukemia | sensitive | Enasidenib | FDA approved - On Companion Diagnostic | Actionable | In a Phase I/II trial that supported FDA approval, Idhifa (enasidenib) treatment resulted in an overall response rate of 40.3% (71/176) with a median response duration of 5.8 months, complete remission in 19.3% (34/176), and stable disease in 48.3% (85/176) of acute myeloid leukemia patients harboring IDH2 mutations (PMID: 28588020; NCT01915498) and IDH2 R172G is on the companion diagnostic. | 28588020 detail... detail... |
| IDH2 R172M | acute myeloid leukemia | sensitive | Enasidenib | FDA approved - On Companion Diagnostic | Actionable | In a Phase I/II trial that supported FDA approval, Idhifa (enasidenib) treatment resulted in an overall response rate of 40.3% (71/176) with a median response duration of 5.8 months, complete remission in 19.3% (34/176), and stable disease in 48.3% (85/176) of acute myeloid leukemia patients harboring IDH2 mutations (PMID: 28588020; NCT01915498) and IDH2 R172M is on the companion diagnostic. | 28588020 detail... detail... |
| IDH2 act mut | cholangiocarcinoma | predicted - sensitive | LY3410738 | Phase I | Actionable | In a Phase I trial, LY3410738 treatment demonstrated safety and resulted in D-2-HG inhibition in patients with IDH-mutant advanced solid tumors, and led to partial response in 1 and stable disease in 22 of 42 patients with relapsed or refractory cholangiocarcinoma and partial response in 3 and stable disease in 9 of 22 patients with glioma (Cancer Res (2023) 83 (8_Supplement): CT098; NCT04521686). | detail... |
| IDH2 act mut | brain glioma | predicted - sensitive | LY3410738 | Phase I | Actionable | In a Phase I trial, LY3410738 treatment demonstrated safety and resulted in D-2-HG inhibition in patients with IDH-mutant advanced solid tumors, and led to partial response in 1 and stable disease in 22 of 42 patients with relapsed or refractory cholangiocarcinoma and partial response in 3 and stable disease in 9 of 22 patients with glioma (Cancer Res (2023) 83 (8_Supplement): CT098; NCT04521686). | detail... |
| IDH2 act mut | acute myeloid leukemia | predicted - sensitive | TQB3455 | Phase I | Actionable | In a Phase I trial, TQB3455 treatment was well tolerated in patients with acute myeloid leukemia harboring IDH2 mutations, and resulted in an objective response rate of 40.63% (13/32, 12 complete remission (CR) or CR with incomplete hematological recovery, 1 partial remission), a median duration of response of 9.17 months, and a median overall survival of 7.43 months (Blood (2022) 140 (Supplement 1): 9082-9083). | detail... |
| IDH2 mutant | acute myeloid leukemia | sensitive | Decitabine | Guideline | Actionable | Dacogen (decitabine) is included in guidelines for adult patients with acute myeloid leukemia harboring an IDH2 mutation (NCCN.org). | detail... |
| IDH2 mutant | acute myeloid leukemia | sensitive | Azacitidine | Guideline | Actionable | Vidaza (azacitidine) is included in guidelines for adult patients with acute myeloid leukemia harboring an IDH2 mutation (NCCN.org). | detail... |
| IDH2 mutant | acute myeloid leukemia | predicted - sensitive | Talazoparib | Preclinical - Patient cell culture | Actionable | In a preclinical study, cells from a patient with acute myeloid leukemia harboring an IDH2 mutation were sensitive to treatment with Talzenna (talazoparib) in culture, demonstrating decreased colony formation (PMID: 29339439). | 29339439 |
| IDH2 mutant | acute myeloid leukemia | predicted - sensitive | Olaparib | Preclinical - Patient cell culture | Actionable | In a preclinical study, cells from a patient with acute myeloid leukemia harboring an IDH2 mutation were sensitive to treatment with Lynparza (olaparib) in culture, demonstrating decreased colony formation (PMID: 29339439). | 29339439 |
| IDH2 mutant | acute myeloid leukemia | predicted - sensitive | Venetoclax | Phase II | Actionable | In a Phase II trial, 33% (4/12) of acute myeloid leukemia patients harboring either IDH1 or IDH2 mutations responded to treatment with Venclexta (venetoclax), demonstrating a complete response or complete response with incomplete blood count recovery (PMID: 27520294). | 27520294 |
| IDH2 mutant | acute myeloid leukemia | sensitive | Decitabine + Venetoclax | Guideline | Actionable | Venclexta (venetoclax) in combination with Dacogen (decitabine) is included in guidelines for adult patients with acute myeloid leukemia harboring an IDH2 mutation (NCCN.org). | detail... |
| IDH2 mutant | acute myeloid leukemia | sensitive | Azacitidine + Venetoclax | Guideline | Actionable | Venclexta (venetoclax) in combination with Vidaza (azacitidine) is included in guidelines for adult patients with acute myeloid leukemia harboring an IDH2 mutation (NCCN.org). | detail... |
| IDH2 mutant | essential thrombocythemia | not applicable | N/A | Guideline | Prognostic | The presence of at least one mutation in either SH2B3, IDH2, U2AF1, SRSF2, SF3B1, EZH2, TP53, or RUNX1 is associated with inferior overall survival in patients with essential thrombocythemia (NCCN.org). | detail... |
| IDH2 mutant | glioblastoma | not applicable | N/A | Guideline | Diagnostic | IDH2 mutations aid in the diagnosis of secondary grade IV glioblastomas (NCCN.org). | detail... |
| IDH2 mutant | malignant astrocytoma | not applicable | N/A | Guideline | Diagnostic | IDH2 mutations aid in the diagnosis of grade II and grade III astrocytomas (NCCN.org). | detail... |
| IDH2 mutant | high grade glioma | not applicable | N/A | Guideline | Diagnostic | IDH2 mutations aid in the diagnosis of gliomas (NCCN.org). | detail... |
| IDH2 mutant | high grade glioma | not applicable | N/A | Guideline | Prognostic | IDH2 mutations are associated with a favorable prognosis in patients with glioma, and are associated with a survival benefit for patients treated with radiation or alkylator therapy (NCCN.org). | detail... |
| IDH2 mutant | anaplastic astrocytoma | not applicable | N/A | Guideline | Diagnostic | IDH2 mutations aid in the diagnosis of grade III astrocytomas (NCCN.org). | detail... |
| IDH2 mutant | oligodendroglioma | not applicable | N/A | Guideline | Diagnostic | IDH2 mutations aid in the diagnosis of oligodendrogliomas (NCCN.org). | detail... |
| IDH2 mutant | myelofibrosis | not applicable | N/A | Guideline | Diagnostic | IDH2 mutations aid in the diagnosis of primary myelofibrosis in the absence of JAK2, CALR, or MPL mutations (NCCN.org). | detail... |
| IDH2 mutant | myelofibrosis | not applicable | N/A | Guideline | Prognostic | IDH2 mutations are associated with inferior leukemia-free survival in patients with myelofibrosis (NCCN.org). | detail... |
| IDH2 mutant | polycythemia vera | not applicable | N/A | Guideline | Prognostic | IDH2 mutations are associated with inferior overall survival and leukemia-free survival in patients with polycythemia vera (NCCN.org). | detail... |
| IDH2 mutant | angioimmunoblastic T-cell lymphoma | not applicable | N/A | Guideline | Diagnostic | IDH2 mutations aid in the diagnosis of angioimmunoblastic T-cell lymphoma (NCCN.org). | detail... |
| IDH2 mutant | hematologic cancer | sensitive | Enasidenib | Phase I | Actionable | In a Phase I study, Enasidenib (AG-221) demonstrated safety and efficacy in patients with hematological cancer harboring IDH2 mutations and included 8 CR, 1 CRp, 3 CRi, and 8 PR (ASH Meeting, Dec 2014, abstract #115). | detail... |
| IDH2 mutant | acute myeloid leukemia | sensitive | Enasidenib | Guideline | Actionable | Idhifa (enasidenib) is included in guidelines for patients with relapsed or refractory acute myeloid leukemia harboring an IDH2 mutation (NCCN.org). | detail... |
| IDH2 mutant | acute myeloid leukemia | sensitive | Enasidenib | FDA approved - Has Companion Diagnostic | Actionable | In a Phase I/II trial that supported FDA approval, Idhifa (enasidenib) treatment resulted in an overall response rate of 40.3% (71/176) with a median response duration of 5.8 months, complete remission in 19.3% (34/176), and stable disease in 48.3% (85/176) of acute myeloid leukemia patients harboring IDH2 mutations (R140Q/L/G/W, R172K/M/G/S/W) (PMID: 28588020; NCT01915498). | 28588020 detail... detail... |
| IDH2 mutant | malignant astrocytoma | predicted - sensitive | Vorasidenib | Phase III | Actionable | In a Phase III trial (INDIGO), Vorasidenib (AG-881) treatment improved progression-free survival (27.7 months vs 11.1 months; HR=0.39, p=0.000000067) and time to next intervention (not reached vs 17.8 months; HR=0.26, p=0.000000019) compared to placebo in patients with astrocytoma or oligodendroglioma harboring IDH1/2 mutations (J Clin Oncol 41, 2023 (suppl 17; abstr LBA1); NCT04164901). | detail... |
| IDH2 mutant | high grade glioma | predicted - sensitive | Vorasidenib | Case Reports/Case Series | Actionable | In a Phase I trial, Vorasidenib (AG-881) treatment resulted in an objective response in 13.6% (3/21, 1 partial response, 2 minor response) and stable disease in 77.3% (17/21) of patients with recurrent or progressive non-enhancing glioma harboring mutations in IDH1 (n=20) or IDH2 (n=1), with 60.5% of the patients remained progression-free and alive at 24 months (J Clin Oncol 38: 2020 (suppl; abstr 2504); NCT02481154). | detail... |
| IDH2 mutant | oligodendroglioma | predicted - sensitive | Vorasidenib | Phase III | Actionable | In a Phase III trial (INDIGO), Vorasidenib (AG-881) treatment improved progression-free survival (27.7 months vs 11.1 months; HR=0.39, p=0.000000067) and time to next intervention (not reached vs 17.8 months, HR=0.26; p=0.000000019) compared to placebo in patients with oligodendroglioma or astrocytoma harboring IDH1/2 mutations (J Clin Oncol 41, 2023 (suppl 17; abstr LBA1); NCT04164901). | detail... |
| IDH2 mutant | acute myeloid leukemia | sensitive | Cytarabine + Venetoclax | Phase Ib/II | Actionable | In a Phase I/II trial, Venclexta (venetoclax) in combination with low-dose cytarabine resulted in complete remission or complete remission with incomplete count recovery in 72% (13/18) of patients with acute myeloid leukemia harboring IDH1 or IDH2 mutations who were ineligible for intensive chemotherapy (ASH Annual Meeting, Dec 2018, Abstract 284; NCT02287233). | detail... |
| IDH2 mutant | acute myeloid leukemia | sensitive | Cytarabine + Venetoclax | Guideline | Actionable | Venclexta (venetoclax) in combination with Cytosar-U (cytarabine) is included in guidelines for adult patients with acute myeloid leukemia harboring an IDH2 mutation (NCCN.org). | detail... |
| IDH2 mutant | acute myeloid leukemia | predicted - sensitive | Daunorubicin + Olaparib | Preclinical - Patient cell culture | Actionable | In a preclinical study, the combination therapy of Lynparza (olaparib) and Cerubidine (daunoruibicin) resulted in an additive effect in cells from a patient with acute myeloid leukemia harboring an IDH2 mutation, demonstrating decreased colony formation in culture (PMID: 29339439). | 29339439 |
| IDH2 mutant | acute myeloid leukemia | predicted - sensitive | Daunorubicin + Talazoparib | Preclinical - Patient cell culture | Actionable | In a preclinical study, the combination therapy of Talzenna (talazoparib) and Cerubidine (daunoruibicin) resulted in an additive effect in cells from a patient with acute myeloid leukemia harboring an IDH2 mutation, demonstrating decreased colony formation in culture (PMID: 29339439). | 29339439 |
| ATRX loss IDH2 mut | malignant astrocytoma | not applicable | N/A | Guideline | Diagnostic | ATRX deficiency in combination with IDH mutation aids in the diagnosis of astrocytoma (NCCN.org). | detail... |
| IDH2 R140L | acute myeloid leukemia | sensitive | Enasidenib | FDA approved - On Companion Diagnostic | Actionable | In a Phase I/II trial that supported FDA approval, Idhifa (enasidenib) treatment resulted in an overall response rate of 40.3% (71/176) with a median response duration of 5.8 months, complete remission in 19.3% (34/176), and stable disease in 48.3% (85/176) of acute myeloid leukemia patients harboring IDH2 mutations (PMID: 28588020; NCT01915498) and IDH2 R140L is on the companion diagnostic. | detail... detail... 28588020 |
| IDH2 R140W | acute myeloid leukemia | sensitive | Enasidenib | FDA approved - On Companion Diagnostic | Actionable | In a Phase I/II trial that supported FDA approval, Idhifa (enasidenib) treatment resulted in an overall response rate of 40.3% (71/176) with a median response duration of 5.8 months, complete remission in 19.3% (34/176), and stable disease in 48.3% (85/176) of acute myeloid leukemia patients harboring IDH2 mutations (PMID: 28588020; NCT01915498) and IDH2 R140W is on the companion diagnostic. | detail... detail... 28588020 |
| IDH2 R172S | acute myeloid leukemia | sensitive | Enasidenib | FDA approved - On Companion Diagnostic | Actionable | In a Phase I/II trial that supported FDA approval, Idhifa (enasidenib) treatment resulted in an overall response rate of 40.3% (71/176) with a median response duration of 5.8 months, complete remission in 19.3% (34/176), and stable disease in 48.3% (85/176) of acute myeloid leukemia patients harboring IDH2 mutations (PMID: 28588020; NCT01915498) and IDH2 R172S is on the companion diagnostic. | 28588020 detail... detail... |
| IDH2 R172S | chondrosarcoma | sensitive | Ceralasertib + Olaparib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Lynparza (olaparib) and Ceralasertib (AZD6738) resulted in a greater decrease in cell viability compared to Ceralasertib (AZD6738) alone in chondrosarcoma cells harboring IDH2 R172S in culture (PMID: 34027408). | 34027408 |
| IDH2 R172W | acute myeloid leukemia | sensitive | Enasidenib | FDA approved - On Companion Diagnostic | Actionable | In a Phase I/II trial that supported FDA approval, Idhifa (enasidenib) treatment resulted in an overall response rate of 40.3% (71/176) with a median response duration of 5.8 months, complete remission in 19.3% (34/176), and stable disease in 48.3% (85/176) of acute myeloid leukemia patients harboring IDH2 mutations (PMID: 28588020; NCT01915498) and IDH2 R172W is on the companion diagnostic. | 28588020 detail... detail... |
| IDH2 R140X | myelodysplastic syndrome | predicted - sensitive | Enasidenib | Phase II | Actionable | In a Phase II trial, Idhifa (enasidenib) treatment was well tolerated and resulted in an overall response rate of 43% (9/21, 5 complete remission (CR), 1 partial remission, 1 marrow CR, 2 hematological improvement only) in patients with higher-risk myelodysplastic syndrome harboring IDH2 R140 or R172 mutations who were refractory to or progressed on hypomethylating agents, with a median overall survival of 21.3 months (J Clin Oncol 39, no. 15_suppl (May 20, 2021) 7010-7010; NCT03383575). | detail... |
| IDH2 R140X | myelodysplastic syndrome | predicted - sensitive | Azacitidine + Enasidenib | Phase II | Actionable | In a Phase II trial, Idhifa (enasidenib) and Vidaza (azacitidine) combination treatment was well tolerated and resulted in an overall response rate of 68% (30/46, 11 complete remission (CR), 3 partial remission, 12 marrow CR, 4 hematological improvement only) in patients with higher-risk myelodysplastic syndrome harboring IDH2 R140 or R172 mutations who were naive to hypomethylating agents, with a median overall survival of 21.3 months (J Clin Oncol 39, no. 15_suppl (May 20, 2021) 7010-7010; NCT03383575). | detail... |
| IDH2 R140X | acute myeloid leukemia | predicted - sensitive | LY3410738 | Phase I | Actionable | In a Phase I trial, LY3410738 demonstrated safety and inhibited D-2-HG in patients with relapsed or refractory IDH-mutant acute myeloid leukemia, resulting in a composite complete remission (CRc) rate of 9% (2/23, 2 CR) in IDH inhibitor-naive patients harbor IDH2 R140 mutations (Cancer Res (2023) 83 (8_Supplement): CT026; NCT04603001). | detail... |
| IDH2 R172X | myelodysplastic syndrome | not applicable | N/A | Guideline | Prognostic | IDH2 R172X is associated with a poor prognosis in patients with myelodysplastic syndrome (NCCN.org). | detail... |
| IDH2 R172X | myelodysplastic syndrome | predicted - sensitive | Enasidenib | Phase II | Actionable | In a Phase II trial, Idhifa (enasidenib) treatment was well tolerated and resulted in an overall response rate of 43% (9/21, 5 complete remission (CR), 1 partial remission, 1 marrow CR, 2 hematological improvement only) in patients with higher-risk myelodysplastic syndrome harboring IDH2 R140 or R172 mutations who were refractory to or progressed on hypomethylating agents, with a median overall survival of 21.3 months (J Clin Oncol 39, no. 15_suppl (May 20, 2021) 7010-7010; NCT03383575). | detail... |
| IDH2 R172X | myelodysplastic syndrome | predicted - sensitive | Azacitidine + Enasidenib | Phase II | Actionable | In a Phase II trial, Idhifa (enasidenib) and Vidaza (azacitidine) combination treatment was well tolerated and resulted in an overall response rate of 68% (30/46, 11 complete remission (CR), 3 partial remission, 12 marrow CR, 4 hematological improvement only) in patients with higher-risk myelodysplastic syndrome harboring IDH2 R140 or R172 mutations who were naive to hypomethylating agents, with a median overall survival of 21.3 months (J Clin Oncol 39, no. 15_suppl (May 20, 2021) 7010-7010; NCT03383575). | detail... |
| IDH2 R172X | acute myeloid leukemia | predicted - sensitive | LY3410738 | Phase I | Actionable | In a Phase I trial, LY3410738 demonstrated safety and inhibited D-2-HG in patients with relapsed or refractory IDH-mutant acute myeloid leukemia, resulting in a composite complete remission (CRc) rate of 46% (6/13, 4 CR, 1 CRh, 1 CRi/CRp) in IDH inhibitor-naive patients harbor IDH2 R172 mutations (Cancer Res (2023) 83 (8_Supplement): CT026; NCT04603001). | detail... |
| IDH2 R140G | acute myeloid leukemia | sensitive | Enasidenib | FDA approved - On Companion Diagnostic | Actionable | In a Phase I/II trial that supported FDA approval, Idhifa (enasidenib) treatment resulted in an overall response rate of 40.3% (71/176) with a median response duration of 5.8 months, complete remission in 19.3% (34/176), and stable disease in 48.3% (85/176) of acute myeloid leukemia patients harboring IDH2 mutations (PMID: 28588020; NCT01915498) and IDH2 R140G is on the companion diagnostic. | detail... detail... 28588020 |
| IDH2 D76fs | acute myeloid leukemia | sensitive | Venetoclax | Case Reports/Case Series | Actionable | In a Phase II trial, an acute myeloid leukemia patient harboring IDH2 D76fs demonstrated sensitivity to treatment with Venclexta (venetoclax), achieving a complete response with incomplete blood count recovery after 24 weeks (PMID: 27520294). | 27520294 |
| IDH2 V305M | malignant epithelioid hemangioendothelioma | predicted - sensitive | Olaparib | Case Reports/Case Series | Actionable | In a Phase II trial (OLAPCO), Lynparza (olaparib) treatment resulted in stable disease lasting 11 months in a patient with pulmonary epithelioid hemangioendothelioma harboring IDH2 V305M (PMID: 34994649, NCT02576444). | 34994649 |
CKB BOOST