{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T22:49:32Z","timestamp":1791413372637,"version":"4.3.3"},"reference-count":34,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"29","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["J Clin Oncol"],"published-print":{"date-parts":[[2026,10,10]]},"abstract":"<jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Smoldering multiple myeloma (SMM) is an asymptomatic but biologically heterogeneous plasma cell disorder with a variable risk of progression to multiple myeloma (MM). Accurate risk stratification is essential as only a subset of patients\u2014defined as high-risk SMM \u2014faces a \u226550% risk of progression within 2 years. Contemporary approaches integrating clinical variables, dynamic biomarkers, genomic alterations, and immune profiling have improved risk assessment although some limitations remain. The therapeutic paradigm of SMM is evolving. Randomized phase III trials have consistently shown that early treatment delays progression to MM. Most recently, daratumumab monotherapy became the first approved treatment for high-risk-SMM following the AQUILA trial, which demonstrated a significant progression-free survival benefit (hazard ratio [HR], 0.49 [95% CI, 0.36 to 0.67],\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; .001) and a trend toward improved overall survival (OS; HR, 0.52 [95% CI, 0.27 to 0.98]) versus observation. This approval challenges the traditional watch-and-wait approach and establishes early intervention as a validated option for selected patients. However, important uncertainties persist. With modern surveillance and advanced imaging, most progression events are asymptomatic and irreversible end-organ damage is uncommon. OS benefit from early treatment remains inconclusive, particularly in the era of quadruplet regimens available at MM progression. In addition, difficulties in precisely identifying truly high-risk patients raise concerns about overtreatment. Emerging data from intensive regimens, bispecific antibodies, and chimeric antigen receptor -T cell therapies suggest that deep and durable responses\u2014and possibly cure\u2014may be achievable in selected patients with high-risk-SMM, but long-term benefit and safety require further study. In conclusion, following the approval of daratumumab, SMM management should be risk-adapted and patient-centered: observation remains appropriate for some patients, while early treatment should be considered for carefully selected high- and ultrahigh-risk individuals.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/jco-26-00236","type":"journal-article","created":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T12:55:41Z","timestamp":1785502541000},"page":"2865-2874","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":0,"title":["High-Risk Smoldering Multiple Myeloma: A Review of Controversies in Early Treatment Versus Observation"],"prefix":"10.1200","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2390-1218","authenticated-orcid":false,"given":"Mar\u00eda-Victoria","family":"Mateos","sequence":"first","affiliation":[{"name":"Hematology Department, Hospital Universitario de Salamanca-IBSAL, CIBERONC and Centro de Investigaci\u00f3n del C\u00e1ncer, IBMCC (USAL-CSIC), Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua","family":"Gustine","sequence":"additional","affiliation":[{"name":"Mass General Brigham Cancer Institute, Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Borja","family":"Puertas","sequence":"additional","affiliation":[{"name":"Hematology Department, Hospital Universitario de Salamanca-IBSAL, CIBERONC and Centro de Investigaci\u00f3n del C\u00e1ncer, IBMCC (USAL-CSIC), Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3066-1275","authenticated-orcid":false,"given":"Noopur","family":"Raje","sequence":"additional","affiliation":[{"name":"Mass General Brigham Cancer Institute, Harvard Medical School, Boston, 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