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000186669 1001_ $$0P:(DE-He78)8dc0876dc3ed1862337d98842984727d$$aGiesen, Nicola$$b0$$eFirst author
000186669 245__ $$aA phase II clinical trial of combined BRAF/MEK inhibition for BRAFV600E-mutated multiple myeloma.
000186669 260__ $$aWashington, DC$$bAmerican Society of Hematology$$c2023
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000186669 500__ $$a#EA:A360#LA:A360# / 2023 Apr 6;141(14):1685-1690
000186669 520__ $$aActivating BRAF mutations are found in a small subset of patients with newly diagnosed multiple myeloma but prevalence increases in late stage, refractory disease, and are associated with adverse outcome. This prospective single-arm, open-label, multicenter phase II 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 (ClinicalTrials.gov identifier: NCT02834364). 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 IMWG criteria. Twelve RRMM patients with a median of 5 prior lines of therapy were enrolled. The overall response rate was 83.3% with 10 patients achieving at least a partial response. The median progression-free survival (PFS) 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 represents a successful targeted precision medicine approach in this disease.
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000186669 7001_ $$aChatterjee, Manik$$b1
000186669 7001_ $$aScheid, Christof$$b2
000186669 7001_ $$aPoos, Alexandra M$$b3
000186669 7001_ $$aBesemer, Britta$$b4
000186669 7001_ $$0P:(DE-He78)b97fc5666ea8f9db9ef499de6b2397cf$$aMiah, Kaya$$b5$$udkfz
000186669 7001_ $$0P:(DE-He78)e15dfa1260625c69d6690a197392a994$$aBenner, Axel$$b6$$udkfz
000186669 7001_ $$aBecker, Nicole$$b7
000186669 7001_ $$00000-0003-1495-8917$$aMoehler, Thomas$$b8
000186669 7001_ $$00000-0003-1699-4313$$aMetzler, Ivana$$b9
000186669 7001_ $$aKhandanpour, Cyrus$$b10
000186669 7001_ $$aSeidel-Glaetzer, Andrea$$b11
000186669 7001_ $$aTrautmann-Grill, Karolin$$b12
000186669 7001_ $$00000-0002-7011-0286$$aKortüm, K Martin$$b13
000186669 7001_ $$aMüller-Tidow, Carsten$$b14
000186669 7001_ $$aMechtersheimer, Gunhild$$b15
000186669 7001_ $$00000-0002-4135-9250$$aGoeppert, Benjamin$$b16
000186669 7001_ $$aStenzinger, Albrecht$$b17
000186669 7001_ $$aWeinhold, Niels$$b18
000186669 7001_ $$aGoldschmidt, Hartmut$$b19
000186669 7001_ $$aWeisel, Katja C$$b20
000186669 7001_ $$0P:(DE-He78)1cb537e833afd985097ccfaddffb2ef3$$aRaab, Marc-Steffen$$b21$$eLast author$$udkfz
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