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Profile Name KMT2A rearrange
Gene Variant Detail

KMT2A rearrange (unknown)

Relevant Treatment Approaches

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Molecular Profile Indication/Tumor Type Response Type Relevant Treatment Approaches Therapy Name Approval Status Evidence Type Efficacy Evidence References
KMT2A rearrange leukemia predicted - sensitive Doxorubicin + I-CBP112 Preclinical Actionable In a preclinical study, I-CBP112 sensitized leukemia cells harboring KMT2A fusions to Doxorubicin, leading to decreased cell growth in culture (PMID: 26552700). 26552700
KMT2A rearrange leukemia predicted - sensitive I-CBP112 + JQ1 Preclinical Actionable In a preclinical study, I-CBP112 sensitized leukemia cells harboring KMT2A fusions to JQ1, resulting in decreased cell growth in culture (PMID: 26552700). 26552700
KMT2A rearrange acute myeloid leukemia not applicable N/A Clinical Study Prognostic In multiple clinical studies, KMT2A rearrangements, specifically partial tandem duplications, were associated with a poor overall survival in acute myeloid leukemia patients (PMID: 24487413, PMID: 22915647, PMID: 22417203, PMID: 21881046). 21881046 24487413 22417203 22915647
KMT2A rearrange acute lymphoblastic leukemia sensitive Cytarabine + Panobinostat Preclinical - Cell culture Actionable In a preclinical study, Farydak (panobinostat) enhanced the effects of Cytosar-U (cytarabine) in acute lymphoblastic leukemia cells harboring a KMT2A rearrangement in culture, resulting in cell death (PMID: 27443263). 27443263
KMT2A rearrange acute lymphoblastic leukemia sensitive Cytarabine + Mocetinostat Preclinical - Cell culture Actionable In a preclinical study, Mocetinostat (MGCD0103) enhanced the effects of Cytosar-U (cytarabine) in acute lymphoblastic leukemia cell lines harboring a KMT2A rearrangement in culture, resulting in cell death (PMID: 27443263). 27443263
KMT2A rearrange acute lymphoblastic leukemia sensitive Cytarabine + Dacinostat Preclinical - Cell culture Actionable In a preclinical study, Dacinostat (LAQ824) enhanced the effects of Cytosar-U (cytarabine) in acute lymphoblastic leukemia cell lines harboring a KMT2A rearrangement in culture, resulting in cell death (PMID: 27443263). 27443263
KMT2A rearrange acute lymphoblastic leukemia sensitive Cytarabine + Romidepsin Preclinical - Cell line xenograft Actionable In a preclinical study, Istodax (romidepsin) enhanced the effects of Cytosar-U (cytarabine) in acute lymphocytic leukemia cell lines harboring a KMT2A rearrangement in culture, and in cell line xenograft models, demonstrating decreased leukemic cells by 73% (PMID: 27443263). 27443263
KMT2A rearrange acute lymphoblastic leukemia decreased response Romidepsin Preclinical - Cell line xenograft Actionable In a preclinical study, Istodax (romidepsin) resulted in minimal activity in acute lymphocytic leukemia cell lines harboring a KMT2A rearrangement in culture, and in cell line xenograft models, demonstrating decreased leukemic cells by 16% (PMID: 27443263). 27443263
KMT2A rearrange acute lymphoblastic leukemia sensitive Cytarabine Preclinical - Cell line xenograft Actionable In a preclinical study, Cytosar-U (cytarabine) decreased leukemic cells by 66% in acute lymphocytic leukemia cell line xenograft models harboring a KMT2A rearrangement (PMID: 27443263). 27443263
KMT2A rearrange acute leukemia predicted - sensitive Pinometostat Case Reports/Case Series Actionable In a Phase I trial, Pinometostat (EPZ-5676) treatment resulted in complete remission in 2 patients with KMT2A rearranged (both with t(11;19)) acute leukemia (PMID: 29724899; NCT01684150). 29724899
KMT2A rearrange acute myeloid leukemia not applicable N/A Guideline Prognostic KMT2A rearrangements (t(v;11q23.3)) are associated with a poor/adverse prognosis in patients with non-APL acute myeloid leukemia (NCCN.org). detail...
KMT2A rearrange childhood B-cell acute lymphoblastic leukemia not applicable N/A Guideline Prognostic KMT2A rearrangements are associated with a poor prognosis in pediatric patients with B-cell acute lymphoblastic leukemia (NCCN.org). detail...
KMT2A rearrange acute myeloid leukemia sensitive CYC065 Preclinical - Cell line xenograft Actionable In a preclinical study, CYC065 (Fadraciclib) treatment resulted in decreased cell viability in an acute myeloid leukemia cell line harboring a KMT2A rearrangement in culture and inhibited tumor growth in a cell line xenograft model (PMID: 32645016). 32645016
KMT2A rearrange acute lymphoblastic leukemia predicted - sensitive CYC065 Preclinical - Cell culture Actionable In a preclinical study, acute lymphoblastic leukemia cell lines harboring KMT2A rearrangements were sensitive to treatment with CYC065 (Fadraciclib) in culture (PMID: 32645016). 32645016
KMT2A rearrange B-cell acute lymphoblastic leukemia not applicable N/A Guideline Prognostic KMT2A rearrangements are associated with a poor prognosis in patients with B-cell acute lymphoblastic leukemia (NCCN.org). detail...
KMT2A rearrange acute leukemia predicted - sensitive Revumenib FDA approved Actionable In a Phase I trial (AUGMENT 101), Revuforj (revumenib) treatment demonstrated acceptable safety and resulted in a complete remission or complete remission with partial hematologic recovery (CR/CRh) rate of 30% (18/60) and median duration of response of 9.1 mo in adult and pediatric patients 1 year or older with acute leukemia harboring KMT2A rearrangements or NPM1 mutations, with a CR/CRh rate of 33% (15/46) and median time to CR/CRh of 2.0 mo in KMT2A rearranged patients (PMID: 36922593; NCT04065399). 36922593 detail...
KMT2A rearrange acute myeloid leukemia predicted - sensitive Revumenib Case Reports/Case Series Actionable In a Phase I trial (AUGMENT-101), Revuforj (revumenib) treatment resulted in an initial response with morphological leukemia-free states in 2 patients with acute myeloid leukemia harboring KMT2A rearrangements (PMID: 36922589; NCT04065399). 36922589
KMT2A rearrange childhood B-cell acute lymphoblastic leukemia predicted - sensitive Blinatumomab Phase II Actionable In a Phase II trial, Blincyto (blinatumomab) treatment followed by a chemotherapy regimen with Cytoxan (cyclophosphamide), Cytosar-U (cytarabine), Mercaptopurine, MARMA, and OCTADAD demonstrated safety and resulted in minimal residual disease-negative or low in 93% (28/30) of infant patients with KMT2A-rearranged, B-precursor, acute lymphoblastic leukemia after infusion with Blincyto (blinatumomab), and a 2-year disease-free survival of 81.6% and an overall survival of 93.3% (PMID: 37099340). 37099340
KMT2A rearrange acute myeloid leukemia sensitive Fingolimod Preclinical - Cell culture Actionable In a preclinical study, Gilenya (fingolimod) inhibited proliferation and induced cell death and cell cycle arrest in an acute myeloid leukemia cell line harboring KMT2A rearrangement in culture (PMID: 37891368). 37891368
KMT2A rearrange acute lymphoblastic leukemia sensitive Fingolimod Preclinical - Cell culture Actionable In a preclinical study, Gilenya (fingolimod) inhibited proliferation and induced cell death and cell cycle arrest in an acute lymphoblastic leukemia cell line harboring KMT2A rearrangement in culture (PMID: 37891368). 37891368
KMT2A rearrange acute myeloid leukemia sensitive Daunorubicin + Fingolimod Preclinical - Patient cell culture Actionable In a preclinical study, treatment with the combination of Gilenya (fingolimod) and Cerubidine (daunorubicin) resulted in cell death in two acute myeloid leukemia cell lines harboring KMT2A rearrangements, and resulted in decreased colony formation in cells derived from a patient-derived xenograft (PDX) model in culture (PMID: 37891368) 37891368
KMT2A rearrange B-cell acute lymphoblastic leukemia not applicable N/A Guideline Diagnostic KMT2A rearrangements (t(v;11q23.3)) aid in the diagnosis of B-cell acute lymphoblastic leukemia (NCCN.org). detail...
KMT2A rearrange acute myeloid leukemia sensitive FHD-286 Preclinical - Patient cell culture Actionable In a preclinical study, FHD-286 induced differentiation and decreased viability in acute myeloid leukemia cell lines and patient-derived cells harboring a KMT2A rearrangement in culture (PMID: 38437498). 38437498
KMT2A rearrange acute myeloid leukemia sensitive Decitabine + FHD-286 Preclinical - Cell culture Actionable In a preclinical study, the combination of FHD-286 and Dacogen (decitabine) synergistically inhibited viability of acute myeloid leukemia cell lines harboring a KMT2A rearrangement in culture (PMID: 38437498). 38437498
KMT2A rearrange acute myeloid leukemia sensitive Birabresib + FHD-286 Preclinical - Patient cell culture Actionable In a preclinical study, the combination of FHD-286 and Birabresib (OTX015) synergistically inhibited viability of acute myeloid leukemia cell lines and a patient-derived cell line harboring a KMT2A rearrangement in culture (PMID: 38437498). 38437498
KMT2A rearrange acute myeloid leukemia sensitive FHD-286 + Revumenib Preclinical - Patient cell culture Actionable In a preclinical study, the combination of FHD-286 and Revuforj (revumenib) synergistically inhibited viability of acute myeloid leukemia cell lines and a patient-derived cell line harboring a KMT2A rearrangement in culture (PMID: 38437498). 38437498
KMT2A rearrange acute myeloid leukemia sensitive FHD-286 + Venetoclax Preclinical - Patient cell culture Actionable In a preclinical study, the combination of FHD-286 and Venclexta (venetoclax) synergistically inhibited viability of acute myeloid leukemia cell lines and a patient-derived cell line harboring a KMT2A rearrangement in culture (PMID: 38437498). 38437498
KMT2A rearrange acute myeloid leukemia no benefit Ziftomenib Phase Ib/II Actionable In a Phase Ib trial (KOMET-001), Ziftomenib treatment resulted in an overall response rate of 17% (3/18) and a complete remission or complete remission with partial hematologic recovery rate of 11% (2/18) at the recommended Phase II dose level in acute myeloid leukemia patients harboring KMT2A rearrangements, but enrollment was halted due to increased frequency of differentiation syndrome (PMID: 39362248; NCT04067336). 39362248