{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T01:54:10Z","timestamp":1789523650204,"version":"build-2803163510"},"reference-count":20,"publisher":"American Society of Hematology","issue":"14","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,4,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Activating BRAF mutations are found in a small subset of patients with newly diagnosed multiple myeloma, but prevalence increases in late-stage, refractory disease, and the mutations are associated with adverse outcome. This prospective single-arm, open-label, multicenter phase 2 trial assessed the efficacy and safety of combined BRAF\/MEK inhibition, using encorafenib and binimetinib, in patients with relapsed\/refractory multiple myeloma (RRMM) carrying a BRAFV600E mutation. Patients received 450 mg encorafenib once daily and binimetinib 45 mg twice daily. The primary end point was the overall response rate achieved within the first year after start of treatment according to International Myeloma Working Group criteria. Twelve RRMM patients with a median of 5\u00a0prior lines of therapy were enrolled. The overall response rate was 83.3%, with 10\u00a0patients achieving at least a partial response. The median progression-free survival was 5.6 months, and overall survival was 55% at 24 months. Emerging resistance to therapy was driven by RAS mutations and structural variants involving the BRAF locus. This is the first prospective clinical trial to demonstrate that combined BRAF\/MEK inhibition is highly effective in patients with BRAFV600E-mutated RRMM, and it represents a successful targeted precision medicine approach in this disease. This trial was registered at www.clinicaltrials.gov as #NCT02834364.<\/jats:p>","DOI":"10.1182\/blood.2022017789","type":"journal-article","created":{"date-parts":[[2023,1,6]],"date-time":"2023-01-06T21:27:14Z","timestamp":1673040434000},"page":"1685-1690","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":49,"title":["A phase 2 clinical trial of combined BRAF\/MEK inhibition for <i>BRAF<\/i>V600E-mutated multiple myeloma"],"prefix":"10.1182","volume":"141","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9615-2564","authenticated-orcid":false,"given":"Nicola","family":"Giesen","sequence":"first","affiliation":[{"name":"1Department of Hematology, Oncology and Rheumatology, Heidelberg University Hospital, Heidelberg, Germany"},{"name":"2Clinical Cooperation Unit (CCU) Molecular Hematology\/Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manik","family":"Chatterjee","sequence":"additional","affiliation":[{"name":"3Comprehensive Cancer Center Mainfranken, University Hospital of W\u00fcrzburg, W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christof","family":"Scheid","sequence":"additional","affiliation":[{"name":"4Department I of Internal Medicine and Center of Integrated Oncology Cologne Bonn, University of Cologne, Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra M.","family":"Poos","sequence":"additional","affiliation":[{"name":"1Department of Hematology, Oncology and Rheumatology, Heidelberg University Hospital, Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Britta","family":"Besemer","sequence":"additional","affiliation":[{"name":"5Department of Hematology, Oncology, Immunology, Rheumatology and Pulmonology, University Hospital of T\u00fcbingen, T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0265-3529","authenticated-orcid":false,"given":"Kaya","family":"Miah","sequence":"additional","affiliation":[{"name":"6Division of Biostatistics, German Cancer Research Center (DKFZ), Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Axel","family":"Benner","sequence":"additional","affiliation":[{"name":"6Division of Biostatistics, German Cancer Research Center (DKFZ), Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Becker","sequence":"additional","affiliation":[{"name":"1Department of Hematology, Oncology and Rheumatology, Heidelberg University Hospital, Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1495-8917","authenticated-orcid":false,"given":"Thomas","family":"Moehler","sequence":"additional","affiliation":[{"name":"7IQVIA, Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1699-4313","authenticated-orcid":false,"given":"Ivana","family":"Metzler","sequence":"additional","affiliation":[{"name":"8Hematology and Oncology, Frankfurt University Medical Center, Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cyrus","family":"Khandanpour","sequence":"additional","affiliation":[{"name":"9Department of Medicine A, Hematology, Oncology and Pneumology, University Hospital M\u00fcnster, M\u00fcnster, Germany"},{"name":"10University Medical Center Schleswig-Holstein Campus L\u03cbbeck, University of L\u03cbbeck, L\u03cbbeck, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Seidel-Glaetzer","sequence":"additional","affiliation":[{"name":"11Coordinating Centre for Clinical Trials (KKS), Heidelberg University, Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karolin","family":"Trautmann-Grill","sequence":"additional","affiliation":[{"name":"12Department of Internal Medicine I, University Hospital Carl Gustav Carus, Technische Universit\u00e4t Dresden, Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7011-0286","authenticated-orcid":false,"given":"K. 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