{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T23:56:28Z","timestamp":1782950188107,"version":"3.54.5"},"reference-count":121,"publisher":"American Society of Hematology","issue":"19","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,5,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Survival of multiple myeloma (MM) has significantly improved over the past decade; however, a composed group of patients (15% to 20%), named high-risk (HR) MM, still experiences reduced survival. Both tumor biology and suboptimal\/absent responses to therapy may underlie HR definition and a clear uniform identification of risk factors is crucial for proper management of these patients. In biologic HRMM, MRD attaining and sustaining negativity, inside and outside bone marrow, should be the primary goal and therapy should be adapted in patients with frailty to reduce toxicity and improve quality of life. MM treatment has traditionally been tailored to age and more recently frailty or comorbidities, but very rarely to the biology of the disease, mainly because of the lack of a clear benefit derived from a specific drug\/combination, inhomogeneity in HR definition, and lack of data coming from prospective, properly designed clinical trials. Some attempts have been successfully made in this direction. In this review, we discuss the current definitions of HR and the need for a consensus, the results of available trials in HR patients, and the way through risk-adapted treatment strategies. For this purpose, we propose several clinical cases of difficult-to-treat patients throughout different treatment phases.<\/jats:p>","DOI":"10.1182\/blood.2020008733","type":"journal-article","created":{"date-parts":[[2021,11,2]],"date-time":"2021-11-02T21:49:26Z","timestamp":1635889766000},"page":"2889-2903","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":43,"title":["How I treat high-risk multiple myeloma"],"prefix":"10.1182","volume":"139","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1422-7305","authenticated-orcid":false,"given":"Elena","family":"Zamagni","sequence":"first","affiliation":[{"name":"IRCCS Azienda Ospedaliero\u2013Universitaria di Bologna, Istituto di Ematologia \u201cSer\u00e0gnoli\u201d Bologna, Italy; and"},{"name":"Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale, Universit\u00e0 di Bologna, Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7828-8230","authenticated-orcid":false,"given":"Simona","family":"Barbato","sequence":"additional","affiliation":[{"name":"IRCCS Azienda Ospedaliero\u2013Universitaria di Bologna, Istituto di Ematologia \u201cSer\u00e0gnoli\u201d Bologna, Italy; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4514-3227","authenticated-orcid":false,"given":"Michele","family":"Cavo","sequence":"additional","affiliation":[{"name":"IRCCS Azienda Ospedaliero\u2013Universitaria di Bologna, Istituto di Ematologia \u201cSer\u00e0gnoli\u201d Bologna, Italy; and"},{"name":"Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale, Universit\u00e0 di Bologna, Bologna, 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