{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T12:42:36Z","timestamp":1775220156870,"version":"3.50.1"},"reference-count":30,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2023,8,9]],"date-time":"2023-08-09T00:00:00Z","timestamp":1691539200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Based on the results obtained in clinical trials, the use of the combination of lenalidomide and dexamethasone (Len\/Dex) has become a potential therapeutic choice for newly diagnosed multiple myeloma (NDMM) ineligible for autologous stem cell transplantation. This study evaluated 89 frail NDMM patients treated with first-line oral association. At the last follow-up, 34 out of 89 patients (38.2%) were alive, and 22 were still in treatment with Len\/Dex. Among 73 evaluable patients who received at least two cycles, the overall response rate was 71% (N = 52). The disease control rate, defined as any level of clinical response to therapy, occurred in 71 patients (97%). We reported one or more adverse events of grade 3 or 4 (G3\/4) in 65.2% (N = 58) of patients, with a prevalence of hematological toxicity (24 patients), leading to an overall discontinuation of treatment in two cases. In univariate analysis, high ISS, high serum \u03b22-microglobulin, and creatinine clearance &lt;30 mL\/min negatively impact OS, while the depth of response positively impacts OS. Moreover, G3-4 anemia, ISS, frailty score, and ECOG negatively impacts PFS. In conclusion, elderly and more frail patients benefit from the Len\/Dex combination also in the era of monoclonal antibodies, ensuring an increased PFS and OS in patients where the therapeutic choice is often limited and usually not very effective.<\/jats:p>","DOI":"10.3390\/cancers15164036","type":"journal-article","created":{"date-parts":[[2023,8,9]],"date-time":"2023-08-09T10:21:50Z","timestamp":1691576510000},"page":"4036","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Lenalidomide plus Dexamethasone Combination as First-Line Oral Therapy of Multiple Myeloma Patients: A Unicentric Real-Life Study"],"prefix":"10.3390","volume":"15","author":[{"given":"Vittorio","family":"Del Fabro","sequence":"first","affiliation":[{"name":"Division of Hematology with BMT, A.O.U. Policlinico \u201cG.Rodolico-San Marco\u201d, 95123 Catania, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mary Ann","family":"Di Giorgio","sequence":"additional","affiliation":[{"name":"Division of Hematology, Azienda Ospedaliera di Rilievo Nazionale e di Alta Specializzazione Garibaldi, 95122 Catania, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valerio","family":"Leotta","sequence":"additional","affiliation":[{"name":"Division of Hematology, Azienda Ospedaliera di Rilievo Nazionale e di Alta Specializzazione Garibaldi, 95122 Catania, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9510-4755","authenticated-orcid":false,"given":"Andrea","family":"Duminuco","sequence":"additional","affiliation":[{"name":"Division of Hematology with BMT, A.O.U. Policlinico \u201cG.Rodolico-San Marco\u201d, 95123 Catania, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudia","family":"Bellofiore","sequence":"additional","affiliation":[{"name":"Division of Hematology, Azienda Ospedaliera di Rilievo Nazionale e di Alta Specializzazione Garibaldi, 95122 Catania, Italy"},{"name":"Amyloidosis Research and Treatment Center, Foundation Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Policlinico San Matteo, 27100 Pavia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0868-5676","authenticated-orcid":false,"given":"Uros","family":"Markovic","sequence":"additional","affiliation":[{"name":"Division of Hematology with BMT, A.O.U. Policlinico \u201cG.Rodolico-San Marco\u201d, 95123 Catania, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandra","family":"Romano","sequence":"additional","affiliation":[{"name":"Division of Hematology with BMT, A.O.U. Policlinico \u201cG.Rodolico-San Marco\u201d, 95123 Catania, Italy"},{"name":"Dipartimento di Chirurgia Generale e Specialit\u00e0 Medico Chirurgiche, University of Catania, 95123 Catania, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Bulla","sequence":"additional","affiliation":[{"name":"Division of Hematology with BMT, A.O.U. Policlinico \u201cG.Rodolico-San Marco\u201d, 95123 Catania, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angelo","family":"Curto Pelle","sequence":"additional","affiliation":[{"name":"Division of Hematology with BMT, A.O.U. Policlinico \u201cG.Rodolico-San Marco\u201d, 95123 Catania, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Federica","family":"Elia","sequence":"additional","affiliation":[{"name":"Division of Hematology with BMT, A.O.U. Policlinico \u201cG.Rodolico-San Marco\u201d, 95123 Catania, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Di Raimondo","sequence":"additional","affiliation":[{"name":"Division of Hematology with BMT, A.O.U. Policlinico \u201cG.Rodolico-San Marco\u201d, 95123 Catania, Italy"},{"name":"Dipartimento di Chirurgia Generale e Specialit\u00e0 Medico Chirurgiche, University of Catania, 95123 Catania, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0862-3598","authenticated-orcid":false,"given":"Concetta","family":"Conticello","sequence":"additional","affiliation":[{"name":"Division of Hematology with BMT, A.O.U. Policlinico \u201cG.Rodolico-San Marco\u201d, 95123 Catania, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e412","DOI":"10.3324\/haematol.2017.183475","article-title":"Dramatically Improved Survival in Multiple Myeloma Patients in the Recent Decade: Results from a Swedish Population-Based Study","volume":"103","author":"Thorsteinsdottir","year":"2018","journal-title":"Haematologica"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1038\/nature13527","article-title":"Structure of the DDB1\u2013CRBN E3 Ubiquitin Ligase in Complex with Thalidomide","volume":"512","author":"Fischer","year":"2014","journal-title":"Nature"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1111\/bjh.12708","article-title":"Immunomodulatory Agents Lenalidomide and Pomalidomide Co-Stimulate T Cells by Inducing Degradation of T Cell Repressors Ikaros and Aiolos via Modulation of the E3 Ubiquitin Ligase Complex CRL4(CRBN.)","volume":"164","author":"Gandhi","year":"2014","journal-title":"Br. J. Haematol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"iv52","DOI":"10.1093\/annonc\/mdx096","article-title":"Multiple Myeloma: ESMO Clinical Practice Guidelines for Diagnosis, Treatment and Follow-Up","volume":"28","author":"Moreau","year":"2017","journal-title":"Ann. Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1056\/NEJMoa0801479","article-title":"Bortezomib plus Melphalan and Prednisone for Initial Treatment of Multiple Myeloma","volume":"359","author":"Schlag","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1016\/S0140-6736(16)31594-X","article-title":"Bortezomib with Lenalidomide and Dexamethasone versus Lenalidomide and Dexamethasone Alone in Patients with Newly Diagnosed Myeloma without Intent for Immediate Autologous Stem-Cell Transplant (SWOG S0777): A Randomised, Open-Label, Phase 3 Trial","volume":"389","author":"Durie","year":"2017","journal-title":"Lancet"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1056\/NEJMoa1402551","article-title":"Lenalidomide and Dexamethasone in Transplant-Ineligible Patients with Myeloma","volume":"371","author":"Benboubker","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_8","first-page":"309","article-title":"Multiple Myeloma: EHA-ESMO Clinical Practice Guidelines for Diagnosis, Treatment and Follow-Up","volume":"5","author":"Dimopoulos","year":"2021","journal-title":"Hemasphere"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1016\/j.clml.2021.06.005","article-title":"Daratumumab Plus Bortezomib, Melphalan, and Prednisone Versus Bortezomib, Melphalan, and Prednisone in Transplant-Ineligible Newly Diagnosed Multiple Myeloma: Frailty Subgroup Analysis of ALCYONE","volume":"21","author":"Mateos","year":"2021","journal-title":"Clin. Lymphoma Myeloma Leuk."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1056\/NEJMoa1714678","article-title":"Daratumumab plus Bortezomib, Melphalan, and Prednisone for Untreated Myeloma","volume":"378","author":"Mateos","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2104","DOI":"10.1056\/NEJMoa1817249","article-title":"Daratumumab plus Lenalidomide and Dexamethasone for Untreated Myeloma","volume":"380","author":"Facon","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_12","first-page":"4","article-title":"Volume 16 Issue 2 Cross Fire: Daratumumab-Based Therapies Are Standard of Care in Newly Diagnosed Multiple Myeloma","volume":"16","author":"Korde","year":"2023","journal-title":"Hematol. Oncol. Stem Cell Ther."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2492","DOI":"10.1080\/10428194.2021.1924369","article-title":"Real-World Analysis of Patient Characteristics, Treatment Outcomes, and Healthcare Resource Utilization across Europe in Patients with Newly Diagnosed Multiple Myeloma Ineligible for Stem Cell Transplantation Who Received Lenalidomide- or Bortezomib-Based Regimens","volume":"62","author":"Zamagni","year":"2021","journal-title":"Leuk. Lymphoma"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3027","DOI":"10.1182\/blood.2020009507","article-title":"Dose\/Schedule-Adjusted Rd-R vs Continuous Rd for Elderly, Intermediate-Fit Patients with Newly Diagnosed Multiple Myeloma","volume":"137","author":"Larocca","year":"2021","journal-title":"Blood"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3616","DOI":"10.1182\/blood.2020008787","article-title":"Oral Ixazomib, Lenalidomide, and Dexamethasone for Transplant-Ineligible Patients with Newly Diagnosed Multiple Myeloma","volume":"137","author":"Facon","year":"2021","journal-title":"Blood"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"136","DOI":"10.3747\/co.20.1252","article-title":"Lenalidomide in Multiple Myeloma\u2014A Practice Guideline","volume":"20","author":"Chen","year":"2013","journal-title":"Curr. Oncol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2863","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":"ref_18","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1038\/s41375-019-0539-0","article-title":"A Simplified Frailty Scale Predicts Outcomes in Transplant-Ineligible Patients with Newly Diagnosed Multiple Myeloma Treated in the FIRST (MM-020) Trial","volume":"34","author":"Facon","year":"2020","journal-title":"Leukemia"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.clml.2011.11.003","article-title":"Observations of Second Primary Malignancy in Patients with Multiple Myeloma","volume":"12","author":"Ormerod","year":"2012","journal-title":"Clin. Lymphoma Myeloma Leuk."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1038\/s41408-020-0273-x","article-title":"Developments in Continuous Therapy and Maintenance Treatment Approaches for Patients with Newly Diagnosed Multiple Myeloma","volume":"10","author":"Dimopoulos","year":"2020","journal-title":"Blood Cancer J."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"826","DOI":"10.3324\/haematol.2014.120121","article-title":"Health-Related Quality-of-Life in Patients with Newly Diagnosed Multiple Myeloma in the FIRST Trial: Lenalidomide plus Low-Dose Dexamethasone versus Melphalan, Prednisone, Thalidomide","volume":"100","author":"Delforge","year":"2015","journal-title":"Haematologica"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1182\/blood-2017-07-795047","article-title":"Final Analysis of Survival Outcomes in the Phase 3 FIRST Trial of Up-Front Treatment for Multiple Myeloma","volume":"131","author":"Facon","year":"2018","journal-title":"Blood"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"107","DOI":"10.3324\/haematol.2014.107714","article-title":"Multiple Myeloma and Infections: A Population-Based Study on 9253 Multiple Myeloma Patients","volume":"100","author":"Blimark","year":"2015","journal-title":"Haematologica"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1157610","DOI":"10.3389\/fonc.2023.1157610","article-title":"Clinical Outcome of SARS-CoV-2 Infections Occurring in Multiple Myeloma Patients after Vaccination and Prophylaxis with Tixagevimab\/Cilgavimab","volume":"13","author":"Duminuco","year":"2023","journal-title":"Front. Oncol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Parisi, M.S., Leotta, S., Romano, A., Del Fabro, V., Martino, E.A., Calafiore, V., Giubbolini, R., Markovic, U., Leotta, V., and Di Giorgio, M.A. (2019). Clinical Benefit of Long-Term Disease Control with Pomalidomide and Dexamethasone in Relapsed\/Refractory Multiple Myeloma Patients. J. Clin. Med., 8.","DOI":"10.3390\/jcm8101695"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.blre.2019.01.001","article-title":"Management of Infectious Complications in Multiple Myeloma Patients: Expert Panel Consensus-Based Recommendations","volume":"34","author":"Girmenia","year":"2019","journal-title":"Blood Rev."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"363","DOI":"10.3324\/haematol.2015.133629","article-title":"Impact of Renal Impairment on Outcomes with Lenalidomide and Dexamethasone Treatment in the FIRST Trial, a Randomized, Open-Label Phase 3 Trial in Transplant-Ineligible Patients with Multiple Myeloma","volume":"101","author":"Dimopoulos","year":"2016","journal-title":"Haematologica"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1038\/s41375-021-01488-8","article-title":"Daratumumab plus Lenalidomide and Dexamethasone in Transplant-Ineligible Newly Diagnosed Multiple Myeloma: Frailty Subgroup Analysis of MAIA","volume":"36","author":"Facon","year":"2022","journal-title":"Leukemia"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1111\/bjh.14213","article-title":"Multiple Myeloma: Patient Outcomes in Real-World Practice","volume":"175","author":"Yong","year":"2016","journal-title":"Br. J. Haematol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2000","DOI":"10.1038\/s41375-020-0876-z","article-title":"Management of Patients with Multiple Myeloma in the Era of COVID-19 Pandemic: A Consensus Paper from the European Myeloma Network (EMN)","volume":"34","author":"Terpos","year":"2020","journal-title":"Leukemia"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/15\/16\/4036\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:29:48Z","timestamp":1760128188000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/15\/16\/4036"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,9]]},"references-count":30,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2023,8]]}},"alternative-id":["cancers15164036"],"URL":"https:\/\/doi.org\/10.3390\/cancers15164036","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,9]]}}}