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Our phase I\/II trial investigated whether adding nelfinavir to lenalidomide\u2013dexamethasone can overcome lenalidomide resistance in lenalidomide-refractory multiple myeloma (MM). Twenty-nine patients were included (high-risk cytogenetic aberrations 31%; \u22652 prior therapy lines 93%; lenalidomide\u2013bortezomib double-refractory 34%). Twenty-four patients (83%) had prior bortezomib and 10 (34%) were lenalidomide\u2013bortezomib double-refractory. They received four cycles of nelfinavir 2500\u2009mg\/day with standard-dose lenalidomide (25\u2009mg days 1\u201321) and dexamethasone (40\/20\u2009mg days 1, 8, 15, 22). Minor response or better was achieved in 16 patients (55%; 95% CI 36\u201374%), including 40% of those who were lenalidomide\u2013bortezomib double-refractory, and partial response or better in nine patients (31%; 95% CI 15\u201351%). Median progression-free survival was 3.4 (95% CI 2.0\u20134.9) months and median overall survival 21.6 (13.0\u201350.1) months. Lenalidomide-related pneumonitis, pneumonia, and neutropenic fever occurred, but there were no unexpected adverse events. Peripheral blood mononuclear cells showed a 45% (95% CI 40\u201351%) reduction in total proteasome activity from baseline and significant induction of unfolded protein response and autophagy. Thus, nelfinavir\u2013lenalidomide\u2013dexamethasone is an active oral combination in lenalidomide-refractory MM.<\/jats:p>","DOI":"10.1038\/s41408-019-0228-2","type":"journal-article","created":{"date-parts":[[2019,8,27]],"date-time":"2019-08-27T17:02:55Z","timestamp":1566925375000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Nelfinavir and lenalidomide\/dexamethasone in patients with lenalidomide-refractory multiple myeloma. 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PS has received consultancy fees or honoraria from Celgene, Takeda, Amgen, Novartis, and Janssen. UM has received consultancy fees, research funding, honoraria from Celgene, as well as honoraria for membership on an entity\u2019s Board of Directors or advisory committees from Celgene.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}],"article-number":"70"}}