Molecular Profile Detail

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Profile Name CSF3R T618I
Gene Variant Detail

CSF3R T618I (gain of function)

Relevant Treatment Approaches JAK Inhibitor (Pan) - ATP competitive

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Molecular Profile Indication/Tumor Type Response Type Relevant Treatment Approaches Therapy Name Approval Status Evidence Type Efficacy Evidence References
CSF3R T618I Advanced Solid Tumor sensitive Ruxolitinib Preclinical - Cell culture Actionable In a preclinical study, Jakafi (ruxolitinib) reduced colony formation of cells expressing CSF3R T618I in culture (PMID: 26475333, PMID: 29977015). 26475333 29977015
CSF3R T618I Advanced Solid Tumor sensitive Ibrutinib Preclinical - Cell culture Actionable In a preclinical study, cells expressing CSF3R T618I were sensitive to treatment with Imbruvica (ibrutinib) in culture, demonstrating a reduced cell proliferation (PMID: 29977015). 29977015
CSF3R T618I Advanced Solid Tumor sensitive Ibrutinib + Ruxolitinib Preclinical - Cell culture Actionable In a preclinical study, the combination of Imbruvica (ibrutinib) and Jakafi (ruxolitinib) resulted in a synergistic effect in cells expressing CSF3R T618I, demonstrating greater decreased cell viability as compared to either agent alone (PMID: 29977015). 29977015
CSF3R T618I hematologic cancer predicted - resistant Dasatinib Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells expressing CSF3R T618I demonstrated resistance to treatment with Sprycel (dasatinib) in culture (PMID: 28031554). 28031554
CSF3R T618I hematologic cancer sensitive Ruxolitinib + Trametinib Preclinical - Cell culture Actionable In a preclinical study, the combination of Jakafi (ruxolitinib) and Mekinist (trametinib) synergized to inhibit colony formation in transformed bone marrow cells expressing CSF3R T618I in culture, and demonstrated improved efficacy over either agent alone (PMID: 29572350). 29572350
CSF3R T618I hematologic cancer no benefit Imatinib Preclinical - Cell culture Actionable In a preclinical study, transformed bone marrow cells expressing CSF3R T618I were not sensitive to Gleevec (imatinib) in culture, demonstrating similar colony formation compared to treatment controls (PMID: 29572350). 29572350
CSF3R T618I hematologic cancer sensitive Trametinib Preclinical - Cell culture Actionable In a preclinical study, Mekinist (trametinib) inhibited colony formation in transformed bone marrow cells expressing CSF3R T618I in culture (PMID: 29572350). 29572350
CSF3R T618I hematologic cancer sensitive Ruxolitinib Preclinical - Cell culture Actionable In a preclinical study, Jakafi (ruxolitinib) inhibited colony formation in transformed bone marrow cells expressing CSF3R T618I in culture (PMID: 29572350). 29572350
CSF3R T618I hematologic cancer sensitive Ruxolitinib Preclinical - Cell culture Actionable In a preclinical study, Jakafi (ruxolitinib) inhibited growth of a transformed cell line expressing CSF3R T618I in culture (PMID: 36579444). 36579444
CSF3R T618I chronic neutrophilic leukemia predicted - sensitive Ruxolitinib Case Reports/Case Series Actionable In a clinical case study, Jakafi (ruxolitinib) treatment resulted in symptom improvement and decreased spleen and liver size lasting 5 months in a patient with chronic neutrophilic leukemia harboring CSF3R T618I along with SETBP1 G870S (PMID: 27068405). 27068405
CSF3R T618I chronic neutrophilic leukemia predicted - sensitive Ruxolitinib Case Reports/Case Series Actionable In a Phase II trial, Jakafi (ruxolitinib) treatment resulted in an overall hematologic response rate of 35% (15/43, 4 complete and 11 partial responses) and a median overall survival of 18.8 months in patients with chronic neutrophilic leukemia (CNL) or atypical chronic myeloid leukemia harboring CSF3R mutations, including T618I (n=20), T640N (n=1), and T615A (n=1), with 2 complete and 9 partial responses in CNL patients harboring CSF3R T618I (PMID: 31880950; NCT02092324). 31880950