{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T20:49:13Z","timestamp":1783111753647,"version":"3.54.6"},"reference-count":16,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2023,8,31]],"date-time":"2023-08-31T00:00:00Z","timestamp":1693440000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Anti-CD38 monoclonal antibody (MoAB) therapy has significantly improved the prognosis of patients with multiple myeloma. However, not all patients sustain durable responses. We aimed to describe the natural history of patients relapsed or refractory (R\/R) to CD38 MoAB therapy. We performed a single-center, retrospective analysis of the clinical characteristics and outcomes of 81 patients with multiple myeloma who progressed after treatment with daratumumab. Our cohort was heavily pretreated, with a median of two lines prior to daratumumab and only 17 patients received daratumumab as a first line. A total of 38.2% had received a previous autologous stem cell transplantation (ASCT), and 61.7% had received both an immunomodulatory drug (IMID) and a proteasome inhibitor (PI). The median overall survival (OS) was 21 months for the global cohort but it decreased to 14 months for triple-class refractory patients and 5 months for penta-refractory patients. Most of the patients (83.9%) received treatment after daratumumab progression, in many cases with second generation IMID or PI, but seven patients were treated with anti-BCMA therapy and three patients received CART therapy within a clinical trial. In conclusion, patients R\/R to daratumumab represent an unmet clinical need with poor prognosis and in need of incorporation of new treatments.<\/jats:p>","DOI":"10.3390\/life13091841","type":"journal-article","created":{"date-parts":[[2023,8,31]],"date-time":"2023-08-31T11:33:25Z","timestamp":1693481605000},"page":"1841","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Clinical Outcomes of Patients with Multiple Myeloma after Daratumumab Failure"],"prefix":"10.3390","volume":"13","author":[{"given":"Irene","family":"Zamanillo","sequence":"first","affiliation":[{"name":"Hematology Department, University Hospital 12 de Octubre, 28041 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Medina de Alba","sequence":"additional","affiliation":[{"name":"Hematology Department, University Hospital 12 de Octubre, 28041 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodrigo","family":"Gil","sequence":"additional","affiliation":[{"name":"Hematology Department, University Hospital 12 de Octubre, 28041 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosalia","family":"de la Puerta","sequence":"additional","affiliation":[{"name":"Hematology Department, University and Polytechnic Hospital, 46026 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael","family":"Alonso","sequence":"additional","affiliation":[{"name":"Hematology Department, University Hospital 12 de Octubre, 28041 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Jimenez-Ubieto","sequence":"additional","affiliation":[{"name":"Hematology Department, University Hospital 12 de Octubre, 28041 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5851-3720","authenticated-orcid":false,"given":"Maria Teresa","family":"Cedena","sequence":"additional","affiliation":[{"name":"Hematology Department, University Hospital 12 de Octubre, 28041 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Calbacho","sequence":"additional","affiliation":[{"name":"Hematology Department, University Hospital 12 de Octubre, 28041 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2699-8353","authenticated-orcid":false,"given":"Rosa","family":"Ayala","sequence":"additional","affiliation":[{"name":"Hematology Department, University Hospital 12 de Octubre, 28041 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7908-0063","authenticated-orcid":false,"given":"Joaquin","family":"Martinez-Lopez","sequence":"additional","affiliation":[{"name":"Hematology Department, University Hospital 12 de Octubre, 28041 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Saltarella, I., Desantis, V., Melaccio, A., Solimando, A.G., Lamanuzzi, A., Ria, R., Storlazzi, C.T., Mariggi\u00f2, M.A., Vacca, A., and Frassanito, M.A. (2020). Mechanisms of Resistance to Anti-CD38 Daratumumab in Multiple Myeloma. Cells, 9.","DOI":"10.3390\/cells9010167"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1182\/blood-2017-06-740944","article-title":"CD38 antibodies in multiple myeloma: Back to the future","volume":"131","author":"Richardson","year":"2018","journal-title":"Blood"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.1056\/NEJMoa1506348","article-title":"Targeting CD38 with Daratumumab Monotherapy in Multiple Myeloma","volume":"373","author":"Lokhorst","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1551","DOI":"10.1016\/S0140-6736(15)01120-4","article-title":"Daratumumab monotherapy in patients with treatment-refractory multiple myeloma (SIRIUS): An open-label, randomised, phase 2 trial","volume":"387","author":"Lonial","year":"2016","journal-title":"Lancet"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1056\/NEJMoa1607751","article-title":"Daratumumab, Lenalidomide, and Dexamethasone for Multiple Myeloma","volume":"375","author":"Dimopoulos","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1056\/NEJMoa1606038","article-title":"Daratumumab, Bortezomib, and Dexamethasone for Multiple Myeloma","volume":"375","author":"Palumbo","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2096","DOI":"10.1016\/S0140-6736(19)32556-5","article-title":"Isatuximab plus pomalidomide and low-dose dexamethasone versus pomalidomide and low-dose dexamethasone in patients with relapsed and refractory multiple myeloma (ICARIA-MM): A randomised, multicentre, open-label, phase 3 study","volume":"394","author":"Attal","year":"2019","journal-title":"Lancet"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1111\/ejh.13046","article-title":"Daratumumab resistance is frequent in advanced-stage multiple myeloma patients irrespective of CD38 expression and is related to dismal prognosis","volume":"100","author":"Pick","year":"2018","journal-title":"Eur. J. Haematol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2266","DOI":"10.1038\/s41375-019-0435-7","article-title":"Outcomes of patients with multiple myeloma refractory to CD38-targeted monoclonal antibody therapy","volume":"33","author":"Gandhi","year":"2019","journal-title":"Leukemia"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1080\/14737140.2020.1828071","article-title":"Current developments in the combination therapy of relapsed\/refractory multiple myeloma","volume":"20","author":"Maples","year":"2020","journal-title":"Expert Rev. Anticancer Ther."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"4691","DOI":"10.1182\/blood-2010-10-299487","article-title":"Consensus recommendations for the uniform reporting of clinical trials: Report of the International Myeloma Workshop Consensus Panel 1","volume":"117","author":"Rajkumar","year":"2011","journal-title":"Blood"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2991","DOI":"10.1002\/cncr.32178","article-title":"Clinical efficacy of daratumumab, pomalidomide, and dexamethasone in patients with relapsed or refractory myeloma: Utility of re-treatment with daratumumab among refractory patients","volume":"125","author":"Nooka","year":"2019","journal-title":"Cancer"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1182\/blood-2017-05-785246","article-title":"Daratumumab plus pomalidomide and dexamethasone in relapsed and\/or refractory multiple myeloma","volume":"130","author":"Chari","year":"2017","journal-title":"Blood"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1146","DOI":"10.1002\/ajh.24883","article-title":"Efficacy of daratumumab-based therapies in patients with relapsed, refractory multiple myeloma treated outside of clinical trials","volume":"92","author":"Lakshman","year":"2017","journal-title":"Am. J. Hematol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1182\/blood-2016-03-705210","article-title":"Clinical efficacy of daratumumab monotherapy in patients with heavily pretreated relapsed or refractory multiple myeloma","volume":"128","author":"Usmani","year":"2016","journal-title":"Blood"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1007\/s40262-017-0598-1","article-title":"Influence of Disease and Patient Characteristics on Daratumumab Exposure and Clinical Outcomes in Relapsed or Refractory Multiple Myeloma","volume":"57","author":"Yan","year":"2017","journal-title":"Clin. Pharmacokinet."}],"container-title":["Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-1729\/13\/9\/1841\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:43:32Z","timestamp":1760129012000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-1729\/13\/9\/1841"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,31]]},"references-count":16,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2023,9]]}},"alternative-id":["life13091841"],"URL":"https:\/\/doi.org\/10.3390\/life13091841","relation":{},"ISSN":["2075-1729"],"issn-type":[{"value":"2075-1729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,31]]}}}