{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T02:35:33Z","timestamp":1789526133367,"version":"build-2803163510"},"reference-count":44,"publisher":"American Society of Hematology","issue":"9","license":[{"start":{"date-parts":[[2022,9,15]],"date-time":"2022-09-15T00:00:00Z","timestamp":1663200000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,3,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>BRAF V600E is the key oncogenic driver mutation in hairy cell leukemia (HCL). We report the efficacy and safety of dabrafenib plus trametinib in patients with relapsed\/refractory BRAF V600E mutation\u2013positive HCL. This open-label, phase 2 study enrolled patients with BRAF V600E mutation\u2013positive HCL refractory to first-line treatment with a purine analog or relapsed after \u22652 prior lines of treatment. Patients received dabrafenib 150 mg twice daily plus trametinib 2 mg once daily until disease progression, unacceptable toxicity, or death. The primary endpoint was investigator-assessed objective response rate (ORR) per criteria adapted from National Comprehensive Cancer Network-Consensus Resolution guidelines. Secondary endpoints included duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety. Fifty-five patients with BRAF V600E mutation\u2013positive HCL were enrolled. The investigator-assessed ORR was 89.0% (95%\u00a0confidence interval, 77.8%-95.9%); 65.5% of patients had a complete response (without minimal residual disease [MRD]: 9.1% [negative immunohistochemistry of bone marrow {BM} biopsy], 12.7% [negative BM aspirate flow cytometry {FC}], 16.4%\u00a0[negative immunohistochemistry and\/or FC results]; with MRD, 49.1%), and 23.6% had a partial response. The 24-month DOR was 97.7% with 24-month PFS and OS rates of 94.4% and 94.5%, respectively. The most common treatment-related adverse events were pyrexia (58.2%), chills (47.3%), and hyperglycemia (40.0%). Dabrafenib plus trametinib demonstrated durable responses with a manageable safety profile consistent with previous observations in other indications and should be considered as a rituximab-free therapeutic option for patients with relapsed\/refractory BRAF V600E mutation\u2013positive HCL. This trial is registered at www.clinicaltrials.gov as #NCT02034110.<\/jats:p>","DOI":"10.1182\/blood.2021013658","type":"journal-article","created":{"date-parts":[[2022,9,15]],"date-time":"2022-09-15T21:59:22Z","timestamp":1663279162000},"page":"996-1006","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":46,"title":["Dabrafenib plus trametinib in patients with relapsed\/refractory<i>BRAF<\/i>V600E mutation\u2013positive hairy cell leukemia"],"prefix":"10.1182","volume":"141","author":[{"given":"Robert J.","family":"Kreitman","sequence":"first","affiliation":[{"name":"1Laboratory of Molecular Biology, National Institutes of Health, Bethesda, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Moreau","sequence":"additional","affiliation":[{"name":"2Department of Hematology, CHU de Nantes, Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farhad","family":"Ravandi","sequence":"additional","affiliation":[{"name":"3Division of Cancer Medicine, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3873-1741","authenticated-orcid":false,"given":"Martin","family":"Hutchings","sequence":"additional","affiliation":[{"name":"4Department of Haematology and Phase 1 Unit, Rigshospitalet, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anas","family":"Gazzah","sequence":"additional","affiliation":[{"name":"5Gustave Roussy Cancer Institute, Villejuif, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne-Sophie","family":"Michallet","sequence":"additional","affiliation":[{"name":"6Centre L\u00e9on B\u00e9rard, Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zev A.","family":"Wainberg","sequence":"additional","affiliation":[{"name":"7Department of Medicine, UCLA, Los Angeles, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9768-0086","authenticated-orcid":false,"given":"Alexander","family":"Stein","sequence":"additional","affiliation":[{"name":"8Department of Internal Medicine II (Oncology Center), University Medical Center Hamburg-Eppendorf, Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0648-1832","authenticated-orcid":false,"given":"Sascha","family":"Dietrich","sequence":"additional","affiliation":[{"name":"9University of Heidelberg, Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maja J. 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