{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T21:08:59Z","timestamp":1792271339903,"version":"4.4.0"},"reference-count":112,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,12,27]],"date-time":"2022-12-27T00:00:00Z","timestamp":1672099200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Medical Science Consulting"},{"name":"Sanofi"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Although lenalidomide-based combinations, such as lenalidomide plus a proteasome inhibitor or an anti-CD38 monoclonal antibody, improve the overall response rate, progression-free survival, and overall survival of patients with relapsed\/refractory multiple myeloma (RRMM), there is a tendency to use these regimens as a frontline treatment. This strategy has led to the development of refractoriness early in the disease course, usually after the patient\u2019s first treatment. Since lenalidomide-free regimens have so far shown limited efficacy in lenalidomide-refractory patients, there is an unmet need for other treatment options. In this review, we discuss the therapeutic options available to treat the general population of lenalidomide-refractory patients (mono, double and triple refractory) and the subpopulation of patients with other high-risk features such as renal failure, extramedullary disease, and high-risk cytogenetics. Moreover, new promising individual therapies and the possible impact of immunotherapy in RRMM patients are debated.<\/jats:p>","DOI":"10.3390\/cancers15010155","type":"journal-article","created":{"date-parts":[[2022,12,28]],"date-time":"2022-12-28T05:30:27Z","timestamp":1672205427000},"page":"155","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["How to Manage Patients with Lenalidomide-Refractory Multiple Myeloma"],"prefix":"10.3390","volume":"15","author":[{"given":"Felipe","family":"de Arriba de la Fuente","sequence":"first","affiliation":[{"name":"Haematology and Medical Oncology Department, Hospital General Universitario Morales Meseguer, Instituto Murciano de Investigaci\u00f3n Biom\u00e9dica (IMIB)-Arrixaca, Universidad de Murcia, 30008 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Montes Gais\u00e1n","sequence":"additional","affiliation":[{"name":"Haematology Department, Hospital Universitario Marqu\u00e9s de Valdecilla, 39008 Cantabria, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8354-768X","authenticated-orcid":false,"given":"Javier","family":"de la Rubia Comos","sequence":"additional","affiliation":[{"name":"Haematology Department, Hospital Universitario y Polit\u00e9cnico La Fe and Universidad Cat\u00f3lica \u201cSan Vicente M\u00e1rtir\u201d, CIBERONC CB16\/12\/00284, 46001 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,27]]},"reference":[{"key":"ref_1","first-page":"470","article-title":"The Diagnosis and Treatment of Multiple Myeloma","volume":"113","author":"Gerecke","year":"2016","journal-title":"Dtsch. 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