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Profile Name | IDH2 R140Q |
Gene Variant Detail | |
Relevant Treatment Approaches | IDH Inhibitor (Pan) IDH2 Inhibitor |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
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 |
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 |
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 - 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 | 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 |
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 | 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 - 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 |
Clinical Trial | Phase | Therapies | Title | Recruitment Status | Covered Countries | Other Countries |
---|---|---|---|---|---|---|
NCT03953898 | Phase II | Olaparib | Using the Anticancer Drug Olaparib to Treat Relapsed/Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome With an Isocitrate Dehydrogenase (IDH) Mutation | Recruiting | USA | 0 |