{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T05:59:09Z","timestamp":1774418349144,"version":"3.50.1"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,3,5]],"date-time":"2021-03-05T00:00:00Z","timestamp":1614902400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004505","name":"Universit\u00e0 di Catania","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004505","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>The anti-CD38 monoclonal antibody daratumumab is approved as a single agent for the treatment of patients with relapsed\/refractory multiple myeloma (RRMM) who received at least three prior lines of therapy, including proteasome inhibitor and immunomodulatory agent. A retrospective multicentric study was designed to evaluate feasibility, tolerability, and efficacy of daratumumab in monotherapy in RRMM.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This study included 44 consecutive RRMM patients that underwent daratumumab monotherapy after a median number of four prior therapies (range 2\u20139). Patients were treated in seven Sicilian centers, as part of Sicilian Myeloma Network and three Calabrian centers outside of controlled clinical trials from August 2016 through July 2020.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The regimen was well tolerated with few grade 3\u20134 haematological and rare non-haematological adverse events, such as pneumonia. Definitive discontinuation was due to disease progression in 25 (57%) patients. Since three patients did not complete at least one full cycle, a total of 41 patients was evaluated for response. Overall response rate was 37%, and the disease control rate (stable disease or better) was high (73%). The best achieved responses within 6 months were very good partial remission or better (27%), partial remission (10%), minimal response (14%) and stable disease (22%). After a median follow up of 7.8 months, median progression free survival (PFS) was 7.2 months and overall survival (OS) 7.8 months. Univariate analysis showed that patients with PR or better after 6 months of therapy had longer median PFS and OS (respectively 29.5 vs 3.6 months, p=0.0001 and 30.6 vs 3.9 months p=0.0001), confirmed by multivariate analysis. Furthermore, standard cytogenetic risk and biochemical relapse type had prolonged median PFS, but not OS (respectively unreached vs 2.6, p=0.03 and 23.9 vs 6.2, p=0.05) in both univariate and multivariate analysis. Additionally, univariate analysis showed that patients treated with carfilzomib-lenalidomide-dexamethasone prior to daratumumab had significantly shorter PFS compared to pomalidomide-dexamethasone (3.4 months vs 9.3 months, p=0.03), that multivariate analysis failed to confirm.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our findings indicate that daratumumab as single agent is safe and well-tolerated regimen in real-life, associated to prolonged PFS and OS in responding patients. No new safety signals were identified.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fonc.2021.624405","type":"journal-article","created":{"date-parts":[[2021,3,5]],"date-time":"2021-03-05T07:05:53Z","timestamp":1614927953000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":13,"title":["Daratumumab as Single Agent in Relapsed\/Refractory Myeloma Patients: A Retrospective Real-Life Survey"],"prefix":"10.3389","volume":"11","author":[{"given":"Uros","family":"Markovic","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandra","family":"Romano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vittorio","family":"Del Fabro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudia","family":"Bellofiore","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Bulla","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marina Silvia","family":"Parisi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Salvatore","family":"Leotta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Massimo","family":"Gentile","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clotilde","family":"Cangialosi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iolanda","family":"Vincelli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giuseppe","family":"Mineo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco","family":"Rossi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Massimo","family":"Poidomani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giuseppina","family":"Uccello","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cinzia","family":"Maugeri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donato","family":"Mannina","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vanessa","family":"Innao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Di Raimondo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Concetta","family":"Conticello","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,3,5]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2011.196","article-title":"Risk of progression and survival in multiple myeloma relapsing after therapy with IMiDs and bortezomib: A multicenter international myeloma working group study","volume":"26","author":"Kumar","year":"2012","journal-title":"Leukemia"},{"key":"B2","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1007\/s11899-019-00507-x","article-title":"Expert Panel Consensus Statement for Proper Evaluation of First Relapse in Multiple Myeloma","volume":"14","author":"Offidani","year":"2019","journal-title":"Curr Hematol Malig Rep"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-11-538835","article-title":"Pomalidomide alone or in combination with low-dose dexamethasone in relapsed and refractory multiple myeloma: A randomized phase 2 study","volume":"123","author":"Richardson","year":"2014","journal-title":"Blood"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(13)70380-2","article-title":"Pomalidomide plus low-dose dexamethasone versus high-dose dexamethasone alone for patients with relapsed and refractory multiple myeloma (MM-003): A randomised, open-label, phase 3 trial","volume":"14","author":"Miguel","year":"2013","journal-title":"Lancet Oncol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-05-425934","article-title":"A phase 2 study of single-agent carfilzomib (PX- 171-003-A1) in patients with relapsed and refractory multiple myeloma","volume":"120","author":"Siegel","year":"2012","journal-title":"Blood"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-11-683854","article-title":"CHAMPION-1: A phase 1\/2 study of once-weekly carfilzomib and dexamethasone for relapsed or refractory multiple myeloma","volume":"127","author":"Berenson","year":"2016","journal-title":"Blood"},{"key":"B7","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/S1470-2045(15)00464-7","article-title":"Carfilzomib and dexamethasone versus bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma (ENDEAVOR): And randomised, phase 3, open-label, multicentre study","volume":"17","author":"Dimopoulos","year":"2016","journal-title":"Lancet Oncol"},{"key":"B8","doi-asserted-by":"publisher","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":"B9","doi-asserted-by":"publisher","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":"B10","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-06-360552","article-title":"A phase 1, multicenter, open-label, dose escalation study of elotuzumab in patients with advanced multiple myeloma","volume":"120","author":"Zonder","year":"2012","journal-title":"Blood"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.3109\/10428194.2012.661175","article-title":"Phase II trial of the pan-deacetylase inhibitor panobinostat as a single agent in advanced relapsed\/refractory multiple myeloma","volume":"53","author":"Wolf","year":"2012","journal-title":"Leuk Lymphoma"},{"key":"B12","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1038\/s41408-018-0141-0","article-title":"Interpreting clinical trial data in multiple myeloma: translating findings to the real-world setting","volume":"8","author":"Richardson","year":"2018","journal-title":"Blood Cancer J"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1003032","article-title":"Daratumumab, a Novel Therapeutic Human CD38 Monoclonal Antibody, Induces Killing of Multiple Myeloma and Other Hematological Tumors","volume":"186","author":"de Weers","year":"2011","journal-title":"J\u00a0Immunol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1080\/19420862.2015.1007813","article-title":"Antibody-mediated phagocytosis contributes to the anti-tumor activity of the therapeutic antibody daratumumab in lymphoma and multiple myeloma","volume":"7","author":"Overdijk","year":"2015","journal-title":"MAbs"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1182\/blood.v124.21.3474.3474","article-title":"Direct in Vitro Comparison of Daratumumab with Surrogate Analogs of CD38 Antibodies MOR03087, SAR650984 and Ab79","author":"Lammerts van Bueren","year":"2014","journal-title":"Blood"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/198539","article-title":"Immunological dysregulation in multiple myeloma microenvironment","volume":"2014","author":"Romano","year":"2014","journal-title":"BioMed Res Int"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1080\/14737159.2018.1470929","article-title":"PMN-MDSC and arginase are increased in myeloma and may contribute to resistance to therapy","volume":"18","author":"Romano","year":"2018","journal-title":"Expert Rev Mol Diagn"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-12-687749","article-title":"Daratumumab depletes CD38+ immune regulatory cells, promotes T-cell expansion, and skews T-cell repertoire in multiple myeloma","volume":"128","author":"Krejcik","year":"2016","journal-title":"Blood"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-16-3192","article-title":"Targeting CD38 suppresses induction and function of T regulatory cells to mitigate immunosuppression in multiple myeloma","volume":"23","author":"Feng","year":"2017","journal-title":"Clin Cancer Res"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.15504","article-title":"Efficacy of retreatment with immunomodulatory drugs and proteasome inhibitors following daratumumab monotherapy in relapsed and refractory multiple myeloma patients","volume":"183","author":"Oostvogels","year":"2018","journal-title":"Br J Haematol"},{"key":"B21","doi-asserted-by":"publisher","first-page":"4996","DOI":"10.1200\/JCO.2010.29.2201","article-title":"American Society of Clinical Oncology\/American Society of Hematology clinical practice guideline update on the use of epoetin and darbepoetin in adult patients with cancer","volume":"28","author":"Rizzo","year":"2010","journal-title":"J Clin Oncol"},{"key":"B22","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.ejca.2010.10.013","article-title":"2010 update of EORTC guidelines for the use of granulocyte-colony stimulating factor to reduce the incidence of chemotherapy-induced febrile neutropenia in adult patients with lymphoproliferative disorders and solid tumours","volume":"47","author":"Aapro","year":"2011","journal-title":"Eur J Cancer"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3026(18)30051-6","article-title":"Beyond maximum grade: modernising the assessment and reporting of adverse events in haematological malignancies","volume":"5","author":"Thanarajasingam","year":"2018","journal-title":"Lancet Haematol"},{"key":"B24","first-page":"71","volume-title":"National Cancer Institute. Common Terminology Criteria for Adverse Events (CTCAE ) version 4.0","year":"2009"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(16)30206-6","article-title":"International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma","volume":"17","author":"Kumar","year":"2016","journal-title":"Lancet Oncol"},{"key":"B26","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1038\/leu.2008.291","article-title":"Criteria for diagnosis, staging, risk stratification and response assessment of multiple myeloma","volume":"23","author":"Kyle","year":"2009","journal-title":"Leukemia"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-02-297325","article-title":"International myeloma working group consensus approach to the treatment of multiple myeloma patients who are candidates for autologous stem cell transplantation","volume":"117","author":"Cavo","year":"2011","journal-title":"Blood"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2018.194118","article-title":"Daratumumab plus bortezomib and dexamethasone versus bortezomib and dexamethasone in relapsed or refractory multiple myeloma: Updated analysis of CASTOR","volume":"103","author":"Spencer","year":"2018","journal-title":"Haematologica"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2018.194282","article-title":"Daratumumab plus lenalidomide and dexamethasone versus lenalidomide and dexamethasone in relapsed or refractory multiple myeloma: Updated analysis of POLLUX","volume":"103","author":"Dimopoulos","year":"2018","journal-title":"Haematologica"},{"key":"B30","doi-asserted-by":"publisher","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":"B31","doi-asserted-by":"publisher","DOI":"10.21873\/anticanres.13712","article-title":"Daratumumab monotherapy in heavily pretreated Asian patients with relapsed and refractory multiple myeloma: A Real-world Experience","volume":"39","author":"Byun","year":"2019","journal-title":"Anticancer Res"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1007\/s00277-019-03655-5","article-title":"Single-agent daratumumab in very advanced relapsed and refractory multiple myeloma patients: a real-life single-center retrospective study","volume":"98","author":"Jullien","year":"2019","journal-title":"Ann Hematol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.5507\/bp.2018.064","article-title":"Single agent daratumumab in advanced multiple myeloma possesses significant efficacy even in an unselected \u201creal-world\u201d population","volume":"163","author":"Minarik","year":"2019","journal-title":"BioMed Pap"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1093\/jjco\/hyy177","article-title":"Brief report: Clinical experiences after emergency use of daratumumab monotherapy for relapsed or refractory multiple myeloma in real practice","volume":"49","author":"Park","year":"2019","journal-title":"Jpn J Clin Oncol"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1016\/j.advms.2019.05.001","article-title":"Efficacy of daratumumab monotherapy in real-world heavily pretreated patients with relapsed or refractory multiple myeloma","volume":"64","author":"Salomon-Perzy\u0144ski","year":"2019","journal-title":"Adv Med Sci"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1309\/74r4-tb90-buwh-27jx","article-title":"Flow Cytometric Immunophenotypic Analysis of 306 Cases of Multiple Myeloma","author":"Lin","year":"2004","journal-title":"Am J Clin Pathol"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2008.07530.x","article-title":"CD4+CD25+FoxP3+ regulatory T cells are increased whilst CD3+CD4-CD8 -\u03b1\u03b2TCR+ Double Negative T cells are decreased in the peripheral blood of patients with multiple myeloma which correlates with disease burden","volume":"144","author":"Feyler","year":"2009","journal-title":"Br J Haematol"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1038\/bcj.2015.32","article-title":"The cellular immune system in myelomagenesis: NK cells and T cells in the development of myeloma [corrected] and their uses in immunotherapies","volume":"5","author":"Dosani","year":"2015","journal-title":"Blood Cancer J"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2018-05-850727","article-title":"IMiDs prime myeloma cells for daratumumab- mediated cytotoxicity through loss of ikaros and aiolos","volume":"132","author":"Fedele","year":"2018","journal-title":"Blood"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.3390\/jcm8060877","article-title":"Feasibility, Tolerability and Efficacy of Carfilzomib in Combination with Lenalidomide and Dexamethasone in Relapsed Refractory Myeloma Patients: A Retrospective Real-Life Survey of the Sicilian Myeloma Network","volume":"8","author":"Conticello","year":"2019","journal-title":"J Clin Med"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-01-631200","article-title":"Treatment of multiple myeloma with high-risk cytogenetics: A consensus of the International Myeloma Working Group","volume":"127","author":"Sonneveld","year":"2016","journal-title":"Blood"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2015.61.2267","article-title":"Revised international staging system for multiple myeloma: A report from international myeloma working group","volume":"33","author":"Palumbo","year":"2015","journal-title":"J Clin Oncol"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.25415","article-title":"Progression with clinical features is associated with worse subsequent survival in multiple myeloma","volume":"94","author":"Chakraborty","year":"2019","journal-title":"Am J Hematol"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.3390\/jcm8101695","article-title":"Clinical Benefit of Long-Term Disease Control with Pomalidomide and Dexamethasone in Relapsed\/Refractory Multiple Myeloma Patients","volume":"8","author":"Parisi","year":"2019","journal-title":"J Clin Med"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2021.624405\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,3,5]],"date-time":"2021-03-05T07:05:57Z","timestamp":1614927957000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2021.624405\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,5]]},"references-count":44,"alternative-id":["10.3389\/fonc.2021.624405"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2021.624405","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,5]]},"article-number":"624405"}}