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Profile Name | BTK C481S |
Gene Variant Detail | |
Relevant Treatment Approaches |
Molecular Profile | Indication/Tumor Type | Response Type | Relevant Treatment Approaches | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|---|
BTK C481S | chronic lymphocytic leukemia/small lymphocytic lymphoma | resistant | Acalabrutinib | Guideline | Actionable | Calquence (acalabrutinib) is not indicated for use in patients with Imbruvica (ibrutinib)-refractory chronic lymphocytic leukemia/small lymphocytic lymphoma harboring BTK C481S (NCCN.org). | detail... | |
BTK C481S | chronic lymphocytic leukemia/small lymphocytic lymphoma | resistant | Zanubrutinib | Guideline | Actionable | Brukinsa (zanubrutinib) is not indicated for use in patients with Imbruvica (ibrutinib)-refractory chronic lymphocytic leukemia/small lymphocytic lymphoma harboring BTK C481S (NCCN.org). | detail... | |
BTK C481S | chronic lymphocytic leukemia | resistant | Ibrutinib | Clinical Study - Cohort | Actionable | In a clinical study, BTK C481S was identified as an acquired mutation in patients with chronic lymphocytic leukemia who relapsed while on Imbruvica (ibrutinib), and was demonstrated to confer resistance to Imbruvica (ibrutinib) in preclinical studies (PMID: 24869598). | 24869598 | |
BTK C481S | mantle cell lymphoma | resistant | Ibrutinib | Case Reports/Case Series | Actionable | In a clinical study, BTK C481S was identified as an acquired mutation that confers resistance to Imbruvica (ibrutinib) in two patients with mantle cell lymphoma who relapsed after a durable response (PMID: 25082755). | 25082755 | |
BTK C481S | chronic lymphocytic leukemia | predicted - resistant | Venetoclax | Case Reports/Case Series | Actionable | In a clinical case study, a patient with chronic lymphocytic leukemia who had relapsed on treatment with Imbruvica (ibrutinib) was treated with Venclexta (venetoclax), but progressed and was found to harbor BTK C481S (PMID: 32232486). | 32232486 | |
BTK C481S | chronic lymphocytic leukemia | predicted - sensitive | Fenebrutinib | Case Reports/Case Series | Actionable | In a Phase I trial, Fenebrutinib (GDC-0853) treatment resulted in clinical activity in patients with chronic lymphocytic leukemia harboring BTK C481S including one patient with a partial response with lymphocytosis and duration of response of 2.5 months and two patients with stable disease, each with a decrease in tumor size from baseline of -44.0% and -23.0% (PMID: 29560128; NCT01991184). | 29560128 | |
BTK C481S | chronic lymphocytic leukemia | predicted - sensitive | Ibrutinib + Selinexor | Case Reports/Case Series | Actionable | In a Phase I trial, Imbruvica (ibrutinib) and Xpovio (selinexor) combination therapy was tolerated and resulted in 1 complete response, 1 partial response, and 7 stable diseases among 9 patients with relapsed or refractory chronic lymphocytic leukemia harboring BTK C481S (PMID: 35608822; NCT02303392). | 35608822 | |
BTK C481S | chronic lymphocytic leukemia | predicted - resistant | Tirabrutinib | Case Reports/Case Series | Actionable | In Phase I trials, a patient with chronic lymphocytic leukemia progressed on treatment with Tirabrutinib (ONO-4059) and was subsequently found to have acquired BTK C481S (PMID: 37257190; NCT01659255 and NCT02457598). | 37257190 | |
BTK C481S | chronic lymphocytic leukemia | predicted - resistant | Acalabrutinib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with chronic lymphocytic leukemia progressed on treatment with Calquence (acalabrutinib), and was subsequently found to have acquired BTK C481S (PMID: 36287227). | 36287227 | |
BTK C481S | chronic lymphocytic leukemia | sensitive | Pirtobrutinib | Case Reports/Case Series | Actionable | In a clinical case study, Jaypirca (pirtobrutinib) resulted in disease control lasting 7 months in a patient with chronic lymphocytic leukemia harboring BTK C481S (PMID: 39048721). | 39048721 | |
BTK C481S | chronic lymphocytic leukemia | sensitive | Duvelisib | Preclinical - Pdx | Actionable | In a preclinical study, Copiktra (duvelisib) treatment resulted in a reduction of leukemia cells in the spleen of a patient-derived xenograft (PDX) model of chronic lymphocytic leukemia harboring BTK C481S (PMID: 37071496). | 37071496 | |
BTK C481S | diffuse large B-cell lymphoma | sensitive | NX-2127 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, NX-2127 inhibited viability of a diffuse large B-cell lymphoma cell line expressing BTK C481S in culture (PMID: 38301010). | 38301010 | |
BTK C481S | diffuse large B-cell lymphoma activated B-cell type | predicted - sensitive | NX-5948 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, NX-5948 treatment resulted in degradation of BTK C481S and inhibited proliferation of an activated B-cell type diffuse large B-cell lymphoma (ABC-DLBCL) cell line harboring BTK C481S in culture and inhibited tumor growth in a cell line xenograft model (Blood 2021 138 (Supp 1):2251). | detail... | |
BTK C481S | diffuse large B-cell lymphoma activated B-cell type | sensitive | AS-1763 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, AS-1763 inhibited proliferation of an activated B cell-like (ABC) diffuse large B-cell lymphoma cell line expressing BTK C481S in culture and inhibited tumor growth in a cell line xenograft model (PMID: 34529443). | 34529443 | |
BTK C481S | diffuse large B-cell lymphoma | predicted - sensitive | ABBV-101 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, ABBV-101 treatment resulted in tumor regression in a cell line xenograft model of diffuse large B-cell lymphoma harboring BTK C481S (Cancer Res (2024) 84 (6_Supplement): 605). | detail... | |
BTK C481S | chronic lymphocytic leukemia | sensitive | ARQ 531 | Preclinical - Patient cell culture | Actionable | In a preclinical study, ARQ 531 treatment inhibited activation of BCR signaling and induced cytotoxicity in Imbruvica (ibrutinib)-resistant patient-derived chronic lymphocytic leukemia cells harboring BTK C481S in culture (PMID: 30093506). | 30093506 | |
BTK C481S | chronic lymphocytic leukemia | resistant | Ibrutinib | Preclinical - Patient cell culture | Actionable | In a preclinical study, primary chronic lymphocytic leukemia cells derived from patients who acquired BTK C481S following Imbruvica (ibrutinib) treatment demonstrated resistance to Imbruvica (ibrutinib) in culture (PMID: 30093506). | 30093506 | |
BTK C481S | chronic lymphocytic leukemia | sensitive | Pirtobrutinib | Preclinical - Patient cell culture | Actionable | In a preclinical study, Jaypirca (pirtobrutinib) inhibited proliferation of patient-derived chronic lymphocytic leukemia cells harboring BTK C481S in culture (PMID: 36287227). | 36287227 | |
BTK C481S | diffuse large B-cell lymphoma | sensitive | Ibrutinib + Venetoclax | Preclinical - Cell culture | Actionable | In a preclinical study, a diffuse large B-cell lymphoma cell line expressing BTK C481S resulting in Imbruvica (ibrutinib) resistance demonstrated increased sensitivity to Imbruvica (ibrutinib) when also treated with Venclexta (venetoclax), demonstrating decreased cell growth in culture (PMID: 28428442). | 28428442 | |
BTK C481S | lymphoma | resistant | Ibrutinib | Preclinical - Cell culture | Actionable | In a preclinical study, lymphoma cells expressing BTK C481S were resistant to Imbruvica (ibrutinib) in culture (PMID: 27626698) | 27626698 | |
BTK C481S | diffuse large B-cell lymphoma | resistant | Ibrutinib | Preclinical - Cell culture | Actionable | In a preclinical study, a diffuse large B-cell lymphoma cell line expressing BTK C481S demonstrated resistance to Imbruvica (ibrutinib) in culture (PMID: 35196427). | 35196427 | |
BTK C481S | diffuse large B-cell lymphoma | sensitive | Pirtobrutinib | Preclinical - Cell culture | Actionable | In a preclinical study, Jaypirca (pirtobrutinib) treatment inhibited viability of a diffuse large B-cell lymphoma cell line harboring BTK C481S in culture (PMID: 35196427). | 35196427 | |
BTK C481S | diffuse large B-cell lymphoma | sensitive | Fenebrutinib | Preclinical - Cell culture | Actionable | In a preclinical study, Fenebrutinib (GDC-0853) treatment inhibited viability of a diffuse large B-cell lymphoma cell line harboring BTK C481S in culture (PMID: 35196427). | 35196427 | |
BTK C481S | diffuse large B-cell lymphoma | sensitive | Vecabrutinib | Preclinical - Cell culture | Actionable | In a preclinical study, Vecabrutinib (SNS-062) treatment inhibited viability of a diffuse large B-cell lymphoma cell line harboring BTK C481S in culture (PMID: 35196427). | 35196427 | |
BTK C481S | diffuse large B-cell lymphoma | sensitive | ARQ 531 | Preclinical - Cell culture | Actionable | In a preclinical study, ARQ 531 treatment inhibited viability of a diffuse large B-cell lymphoma cell line harboring BTK C481S in culture (PMID: 35196427). | 35196427 | |
BTK C481S | mantle cell lymphoma | predicted - resistant | Edralbrutinib | Preclinical - Cell culture | Actionable | In a preclinical study, Edralbrutinib (TG-1701) treatment resulted in reduced sensitivity in a mantle cell lymphoma cell line expressing BTK C481S compared to the parental wild-type BTK cell line in culture (PMID: 34551904). | 34551904 | |
BTK C481S | chronic lymphocytic leukemia | sensitive | Vecabrutinib | Preclinical - Cell culture | Actionable | In a preclinical study, Vecabrutinib (SNS-062) inhibited viability of a chronic lymphocytic leukemia cell line harboring BTK C481S (PMID: 34662393). | 34662393 | |
BTK C481S | diffuse large B-cell lymphoma | predicted - sensitive | NX-5948 | Preclinical - Cell culture | Actionable | In a preclinical study, NX-5948 inhibited Btk signaling and proliferation of a diffuse large B-cell lymphoma cell line expressing BTK C481S in culture (Cancer Res (2023) 83 (7_Supplement): 2850). | detail... | |
BTK C481S | diffuse large B-cell lymphoma | resistant | Ibrutinib | Preclinical - Cell culture | Actionable | In a preclinical study, diffuse large B-cell lymphoma cell lines expressing BTK C481S demonstrated resistance to Imbruvica (ibrutinib) in culture (PMID: 36183831). | 36183831 | |
BTK C481S | diffuse large B-cell lymphoma | resistant | Zanubrutinib | Preclinical - Cell culture | Actionable | In a preclinical study, a diffuse large B-cell lymphoma cell line expressing BTK C481S demonstrated resistance to Brukinsa (zanubrutinib) in culture (PMID: 38301010). | 38301010 | |
BTK C481S | diffuse large B-cell lymphoma | resistant | Acalabrutinib | Preclinical - Cell culture | Actionable | In a preclinical study, a diffuse large B-cell lymphoma cell line expressing BTK C481S demonstrated resistance to Calquence (acalabrutinib) in culture (PMID: 38301010). | 38301010 | |
BTK C481S | diffuse large B-cell lymphoma | resistant | Ibrutinib | Preclinical - Cell culture | Actionable | In a preclinical study, a diffuse large B-cell lymphoma cell line expressing BTK C481S demonstrated resistance to Imbruvica (ibrutinib) in culture (PMID: 38301010). | 38301010 | |
BTK C481S | lymphoma | predicted - sensitive | DZD8586 | Preclinical - Cell culture | Actionable | In a preclinical study, DZD8586 inhibited proliferation of lymphoma cells expressing BTK C481S in culture (Blood (2023) 142 (Supplement 1): 2822). | detail... | |
BTK C481S | diffuse large B-cell lymphoma | predicted - sensitive | ONO-7018 | Preclinical - Cell culture | Actionable | In a preclinical study, ONO-7018 inhibited proliferation of a diffuse large B-cell lymphoma cell line expressing BTK C481S in culture (Blood (2023) 142 (Supplement 1): 5779). | detail... | |
BTK C481S | Advanced Solid Tumor | predicted - sensitive | RN486 | Preclinical - Biochemical | Actionable | In a preclinical study, treatment with RN486 resulted in reduced Btk activity in a cell line expressing BTK C481S in culture (PMID: 33526860). | 33526860 | |
BTK C481S | Advanced Solid Tumor | predicted - sensitive | Fenebrutinib | Preclinical - Biochemical | Actionable | In a preclinical study, treatment with Fenebrutinib resulted in reduced Btk activity in a cell line expressing BTK C481S in culture (PMID: 33526860). | 33526860 | |
BTK C481S | chronic lymphocytic leukemia | predicted - sensitive | ABBV-101 | Preclinical | Actionable | In a preclinical study, ABBV-101 treatment resulted in reduced tumor burden in the spleen and lymph nodes and decreased leukemic burden in the blood compartment of a mouse model of chronic lymphocytic leukemia harboring BTK C481S (Cancer Res (2024) 84 (6_Supplement): 605). | detail... |
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