Molecular Profile Detail

Profile Name IDH2 R172K
Gene Variant Detail

IDH2 R172K (gain of function)

Relevant Treatment Approaches IDH Inhibitor (Pan) IDH2 Inhibitor

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Molecular Profile Indication/Tumor Type Response Type Relevant Treatment Approaches Therapy Name Approval Status Evidence Type Efficacy Evidence References
IDH2 R140Q IDH2 I319M acute myeloid leukemia resistant IDH2 Inhibitor 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
IDH2 R140W FLT3 Y599_D600insSTDNEYFYVDFREYEY acute myeloid leukemia predicted - sensitive IDH2 Inhibitor Enasidenib + Quizartinib Preclinical Actionable In a preclinical study, the combination of Enasidenib (AG-221) and Quizartinib (AC220) 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...
IDH2 R140Q glioblastoma multiforme predicted - sensitive IDH2 Inhibitor 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 malignant glioma predicted - sensitive IDH Inhibitor (Pan) AG-881 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 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 acute myeloid leukemia sensitive IDH2 Inhibitor 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 acute myeloid leukemia sensitive IDH2 Inhibitor 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 IDH2 Q316E acute myeloid leukemia resistant IDH2 Inhibitor 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 D76fs acute myeloid leukemia sensitive Venetoclax Phase II 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 mutant hematologic cancer sensitive IDH2 Inhibitor 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 grade III astrocytoma not applicable N/A Guideline Diagnostic IDH2 mutations aid in the diagnosis of grade III astrocytomas (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 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 oligodendroglioma not applicable N/A Guideline Diagnostic IDH2 mutations aid in the diagnosis of oligodendrogliomas (NCCN.org). detail...
IDH2 mutant malignant glioma not applicable N/A Guideline Diagnostic IDH2 mutations aid in the diagnosis of gliomas (NCCN.org). detail...
IDH2 mutant malignant 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 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 essential thrombocythemia not applicable N/A Guideline Prognostic The presence of at least one mutation in either SH2B3, IDH2, U2AF1, SF3B1, EZH2, or TP53 is associated with inferior overall survival in patients with essential thrombocythemia (NCCN.org). detail...
IDH2 mutant acute myeloid leukemia sensitive IDH2 Inhibitor 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 IDH2 Inhibitor Enasidenib FDA approved 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). 28588020
IDH2 mutant acute myeloid leukemia predicted - 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 glioblastoma multiforme not applicable N/A Guideline Diagnostic IDH2 mutations aid in the diagnosis of secondary grade IV glioblastomas (NCCN.org). detail...
ATRX loss IDH2 mut astrocytoma not applicable N/A Guideline Diagnostic ATRX deficiency in combination with IDH mutation aids in the diagnosis of astrocytoma (NCCN.org). detail...
IDH2 R172K KRAS G12D intrahepatic cholangiocarcinoma sensitive Dasatinib Preclinical Actionable In a preclinical study, intrahepatic cholangiocarcinoma cells harboring IDH2 R172K and KRAS G12D demonstrated increased sensitivity to Sprycel (dasatinib) induced growth inhibition in culture and in xenograft models (PMID: 27231123). 27231123
IDH2 R172K KRAS G12D intrahepatic cholangiocarcinoma sensitive Saracatinib Preclinical Actionable In a preclinical study, intrahepatic cholangiocarcinoma cells harboring IDH2 R172K and KRAS G12D demonstrated increased sensitivity to Saracatinib (AZD0530) induced growth inhibition in culture (PMID: 27231123). 27231123
IDH2 R172K acute myeloid leukemia sensitive IDH2 Inhibitor 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 IDH2 Inhibitor Enasidenib Preclinical - Cell culture 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 glioblastoma multiforme predicted - sensitive IDH2 Inhibitor Enasidenib Preclinical - Cell culture 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 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 wild-type malignant 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...
Clinical Trial Phase Therapies Title Recruitment Status