{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T08:40:14Z","timestamp":1781080814666,"version":"3.54.1"},"reference-count":87,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2021,1,22]],"date-time":"2021-01-22T00:00:00Z","timestamp":1611273600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010661","name":"Horizon 2020","doi-asserted-by":"publisher","award":["817997"],"award-info":[{"award-number":["817997"]}],"id":[{"id":"10.13039\/100010661","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Smoldering multiple myeloma (SMM), an asymptomatic plasma cell neoplasm, is currently diagnosed according to the updated IMWG criteria, which reflect an intermediate tumor mass between monoclonal gammopathy of undetermined significance (MGUS) and active MM. However, SMM is a heterogeneous entity and individual case may go from an \u201cMGUS-like\u201d behavior to \u201cearly MM\u201d with rapid transformation into symptomatic disease. This wide range of clinical outcomes poses challenges for prognostication and management of individual patients. However, initial studies showed a benefit in terms of progression or even survival for early treatment of high-risk SMM patients. While outside of clinical trials the conventional approach to SMM generally remains that of close observation, these studies raised the question of whether early treatment should be offered in high-risk patients, prompting evaluation of several different therapeutic approaches with different goals. While delay of progression to MM with a non-toxic treatment is clearly achievable by early treatment, a convincing survival benefit still needs to be proven by independent studies. Furthermore, if SMM is to be considered less biologically complex than MM, early treatment may offer the chance of cure that is currently not within reach of any active MM treatment. In this paper, we present updated results of completed or ongoing clinical trials in SMM treatment, highlighting areas of uncertainty and critical issues that will need to be addressed in the near future before the \u201cwatch and wait\u201d paradigm in SMM is abandoned in favor of early treatment.<\/jats:p>","DOI":"10.3390\/jcm10030421","type":"journal-article","created":{"date-parts":[[2021,1,22]],"date-time":"2021-01-22T11:13:53Z","timestamp":1611314033000},"page":"421","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["What Is New in the Treatment of Smoldering Multiple Myeloma?"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1018-5139","authenticated-orcid":false,"given":"Niccolo\u2019","family":"Bolli","sequence":"first","affiliation":[{"name":"Division of Hematology, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milano, Italy"},{"name":"Department of Oncology and Onco-Hematology, University of Milan, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Sgherza","sequence":"additional","affiliation":[{"name":"Unit of Hematology and Stem Cell Transplantation, AOUC Policlinico, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Curci","sequence":"additional","affiliation":[{"name":"Unit of Hematology and Stem Cell Transplantation, AOUC Policlinico, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2557-1235","authenticated-orcid":false,"given":"Rita","family":"Rizzi","sequence":"additional","affiliation":[{"name":"Unit of Hematology and Stem Cell Transplantation, AOUC Policlinico, 70124 Bari, Italy"},{"name":"Department of Emergency and Organ Transplantation, \u201cAldo Moro\u201d University School of Medicine, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0256-0146","authenticated-orcid":false,"given":"Vanda","family":"Strafella","sequence":"additional","affiliation":[{"name":"Department of Emergency and Organ Transplantation, \u201cAldo Moro\u201d University School of Medicine, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6486-8912","authenticated-orcid":false,"given":"Mario","family":"Delia","sequence":"additional","affiliation":[{"name":"Unit of Hematology and Stem Cell Transplantation, AOUC Policlinico, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vito Pier","family":"Gagliardi","sequence":"additional","affiliation":[{"name":"Unit of Hematology and Stem Cell Transplantation, AOUC Policlinico, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonino","family":"Neri","sequence":"additional","affiliation":[{"name":"Division of Hematology, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milano, Italy"},{"name":"Department of Oncology and Onco-Hematology, University of Milan, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Baldini","sequence":"additional","affiliation":[{"name":"Division of Hematology, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milano, Italy"},{"name":"Department of Oncology and Onco-Hematology, University of Milan, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7926-6052","authenticated-orcid":false,"given":"Francesco","family":"Albano","sequence":"additional","affiliation":[{"name":"Unit of Hematology and Stem Cell Transplantation, AOUC Policlinico, 70124 Bari, Italy"},{"name":"Department of Emergency and Organ Transplantation, \u201cAldo Moro\u201d University School of Medicine, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pellegrino","family":"Musto","sequence":"additional","affiliation":[{"name":"Unit of Hematology and Stem Cell Transplantation, AOUC Policlinico, 70124 Bari, Italy"},{"name":"Department of Emergency and Organ Transplantation, \u201cAldo Moro\u201d University School of Medicine, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,1,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1347","DOI":"10.1056\/NEJM198006123022405","article-title":"Smoldering Multiple Myeloma","volume":"302","author":"Kyle","year":"1980","journal-title":"N. 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