{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T03:57:27Z","timestamp":1793246247594,"version":"4.5.0"},"reference-count":129,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,2,25]],"date-time":"2021-02-25T00:00:00Z","timestamp":1614211200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81172257"],"award-info":[{"award-number":["81172257"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005240","name":"Changjiang Scholar Program of Chinese Ministry of Education","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005240","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:p>The increasing incidence of geriatric patients with multiple myeloma has elevated concerns in clinical practice. While the introduction of novel therapeutic agents has substantially improved outcomes in younger patients with myeloma, poorer outcomes remain in older patients. Managing older patients requires a multidisciplinary team approach to consider factors that may influence both treatment selection and outcomes. Aging is associated with remodeling of vital organs, physiological downregulations of basal metabolism, susceptibility to multiple comorbidities with ultimate frailty, thereby contributing to the underrepresentation and exclusion of very old patients from clinical trials. Therefore, timely confirmation of a precise diagnosis is crucial for prompt initiation of treatment if the desired outcome is to be achieved. Adequate and judicious assessment using comprehensive geriatric assessment tools minimizes toxicities and treatment discontinuation. Initiating treatment with combinational therapy requires knowledge of indications and anticipated outcomes, as well as individualized therapy with appropriate dose-adjustment. Individualized therapy based on good clinical acumen and best practices obverts unwanted polypharmacy, preventing iatrogenic harm. This review will therefore address the approaches and challenges faced in managing myeloma in geriatric patients aged 80 years and older, highlighting recommended therapeutic strategies and future prospective regimens.<\/jats:p>","DOI":"10.3389\/fmed.2021.612696","type":"journal-article","created":{"date-parts":[[2021,2,25]],"date-time":"2021-02-25T07:30:34Z","timestamp":1614238234000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":33,"title":["Approaches and Challenges in the Management of Multiple Myeloma in the Very Old: Future Treatment Prospects"],"prefix":"10.3389","volume":"8","author":[{"given":"Natasha Mupeta","family":"Kaweme","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geoffrey Joseph","family":"Changwe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuling","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,2,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"423","DOI":"10.2147\/CIA.S89465","article-title":"Multiple myeloma in the very elderly patient: challenges and solutions","volume":"2016","author":"King","year":"2016","journal-title":"CIA."},{"key":"B2","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1007\/s11899-019-00500-4","article-title":"Challenges and strategies in the management of multiple myeloma in the elderly population","volume":"14","author":"Zanwar","year":"2019","journal-title":"Curr Hematol Malig Rep."},{"key":"B3","doi-asserted-by":"publisher","first-page":"2179","DOI":"10.1182\/blood-2015-05-612960","article-title":"How I treat fragile myeloma patients","volume":"126","author":"Larocca","year":"2015","journal-title":"Blood."},{"key":"B4","doi-asserted-by":"publisher","first-page":"488","DOI":"10.1182\/asheducation-2013.1.488","article-title":"How should we treat newly diagnosed multiple myeloma patients?","volume":"2013","author":"Mateos","year":"2013","journal-title":"Hematology."},{"key":"B5","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1093\/jnci\/dju067","article-title":"Multiple myeloma in the very old: an IASIA conference report","volume":"106","author":"Tuchman","year":"2014","journal-title":"J Natl Cancer Inst."},{"key":"B6","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1111\/ejh.13530","article-title":"Survival trends in elderly myeloma patients","volume":"106","author":"Jones","year":"2020","journal-title":"Eur J Haematol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"575","DOI":"10.14694\/EDBK_175171","article-title":"Myeloma in elderly patients: when less is more and more is more","volume":"37","author":"Rosko","year":"2017","journal-title":"Am Soc Clin Oncol Educ Book."},{"key":"B8","doi-asserted-by":"publisher","first-page":"3669","DOI":"10.7759\/cureus.3669","article-title":"Treatment of multiple myeloma in elderly patients: a review of literature and practice guidelines","volume":"10","author":"Manapuram","year":"2018","journal-title":"Cureus."},{"key":"B9","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1007\/s11912-019-0804-4","article-title":"Management of newly diagnosed elderly multiple myeloma patients","volume":"21","author":"Antoine-Pepeljugoski","year":"2019","journal-title":"Curr Oncol Rep."},{"key":"B10","doi-asserted-by":"publisher","first-page":"3921","DOI":"10.1200\/JCO.2014.58.7618","article-title":"Community-based phase IIIB trial of three UPFRONT bortezomib-based myeloma regimens","volume":"33","author":"Niesvizky","year":"2015","journal-title":"JCO."},{"key":"B11","doi-asserted-by":"publisher","first-page":"1133","DOI":"10.3324\/haematol.2014.110296","article-title":"Age and aging in blood disorders: multiple myeloma","volume":"99","author":"Zweegman","year":"2014","journal-title":"Haematologica."},{"key":"B12","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1136\/pgmj.2006.048587","article-title":"Understanding frailty","volume":"83","author":"Lally","year":"2007","journal-title":"Postgraduate Med J."},{"key":"B13","doi-asserted-by":"publisher","first-page":"1046","DOI":"10.1056\/NEJMra1011442","article-title":"Multiple Myeloma","volume":"364","author":"Palumbo","year":"2011","journal-title":"N Engl J Med."},{"key":"B14","doi-asserted-by":"publisher","first-page":"2068","DOI":"10.1182\/blood-2014-12-615187","article-title":"Geriatric assessment predicts survival and toxicities in elderly myeloma patients: an international myeloma working group report","volume":"125","author":"Palumbo","year":"2015","journal-title":"Blood."},{"key":"B15","doi-asserted-by":"publisher","first-page":"1091","DOI":"10.1002\/ajh.25117","article-title":"Multiple myeloma: 2018. Update on diagnosis, risk-stratification, and management","volume":"93","author":"Rajkumar","year":"2018","journal-title":"Am J Hematol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"1362","DOI":"10.1056\/NEJMoa054494","article-title":"Prevalence of monoclonal gammopathy of undetermined significance","volume":"354","author":"Kyle","year":"2006","journal-title":"N Engl J Med."},{"key":"B17","doi-asserted-by":"publisher","first-page":"e352","DOI":"10.1016\/j.clml.2020.01.017","article-title":"Consensus guidelines on the diagnosis of multiple myeloma and related disorders: recommendations of the myeloma Canada research network consensus guideline consortium","volume":"20","author":"Bergstrom","year":"2020","journal-title":"Clin Lymphoma Myeloma Leukemia."},{"key":"B18","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1159\/000442511","article-title":"Current trends of renal impairment in multiple myeloma","volume":"1","author":"Yadav","year":"2016","journal-title":"Kidney Dis."},{"key":"B19","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1002\/ajh.24291","article-title":"Bone marrow infiltration by multiple myeloma causes anemia by reversible disruption of erythropoiesis","volume":"91","author":"Bouchnita","year":"2016","journal-title":"Am J Hematol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12885-020-6596-y","article-title":"Bone complications in patients with multiple myeloma in five European Countries: a retrospective patient chart review","volume":"20","author":"Mateos","year":"2020","journal-title":"BMC Cancer."},{"key":"B21","doi-asserted-by":"publisher","first-page":"e019758","DOI":"10.1136\/bmjopen-2017-019758","article-title":"Quantifying intervals to diagnosis in myeloma: a systematic review and meta-analysis","volume":"8","author":"Koshiaris","year":"2018","journal-title":"BMJ Open."},{"key":"B22","doi-asserted-by":"publisher","first-page":"e538","DOI":"10.1016\/S1470-2045(14)70442-5","article-title":"International myeloma working group updated criteria for the diagnosis of multiple myeloma","volume":"15","author":"Rajkumar","year":"2014","journal-title":"Lancet Oncol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1002\/hon.2586","article-title":"Multiple myeloma: every year a new standard?","volume":"37","author":"Rajkumar","year":"2019","journal-title":"Hematol Oncol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"2955","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":"B25","doi-asserted-by":"publisher","first-page":"500","DOI":"10.1200\/EDBK_239067","article-title":"Approach to the older adult with multiple myeloma","volume":"39","author":"Mina","year":"2019","journal-title":"Am Soc Clin Oncol Educ Book."},{"key":"B26","doi-asserted-by":"publisher","first-page":"M255","DOI":"10.1093\/gerona\/59.3.M255","article-title":"Untangling the concepts of disability, frailty, and comorbidity: implications for improved targeting and care","volume":"59","author":"Fried","year":"2004","journal-title":"J Gerontol Series A Biol Sci Med Sci."},{"key":"B27","doi-asserted-by":"publisher","first-page":"e437","DOI":"10.1016\/S1470-2045(12)70259-0","article-title":"Frailty screening methods for predicting outcome of a comprehensive geriatric assessment in elderly patients with cancer: a systematic review","volume":"13","author":"Hamaker","year":"2012","journal-title":"Lancet Oncol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"130","DOI":"10.4103\/0366-6999.197977","article-title":"Geriatric assessment to predict survival and risk of serious adverse events in elderly newly diagnosed multiple myeloma patients: a multicenter study in China","volume":"130","author":"Zhong","year":"2017","journal-title":"Chin Med"},{"key":"B29","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1016\/j.bjhh.2015.03.007","article-title":"Limitations of performance status assessment in elderly with acute myeloid leukemia","volume":"37","author":"Carbonell","year":"2015","journal-title":"Rev Bras Hematol Hemoter"},{"key":"B30","doi-asserted-by":"publisher","first-page":"515","DOI":"10.1182\/blood-2017-09-746420","article-title":"Frailty and the management of hematologic malignancies","volume":"131","author":"Abel","year":"2018","journal-title":"Blood"},{"key":"B31","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1182\/asheducation-2013.1.158","article-title":"Treatment of older patients with chronic lymphocytic leukemia: key questions and current answers","author":"Shanafelt","year":"2013","journal-title":"Hematol Am Soc Hematol Educ Program"},{"key":"B32","doi-asserted-by":"publisher","first-page":"437852","DOI":"10.1155\/2014\/437852","article-title":"Comparison of the Freiburg and Charlson comorbidity indices in predicting overall survival in elderly patients with newly diagnosed multiple myeloma","volume":"2014","author":"Kim","year":"2014","journal-title":"Biomed Res Int"},{"key":"B33","doi-asserted-by":"publisher","first-page":"416","DOI":"10.1016\/j.clml.2015.03.004","article-title":"Prognostic effect of comorbidity indices in elderly patients with multiple myeloma","volume":"15","author":"Bila","year":"2015","journal-title":"Clin Lymphoma Myeloma Leuk"},{"key":"B34","doi-asserted-by":"publisher","first-page":"1807","DOI":"10.1002\/cam4.1128","article-title":"The impact of comorbidity on mortality in multiple myeloma: a Danish nationwide population?based study","volume":"6","author":"Gregersen","year":"2017","journal-title":"Cancer Med"},{"key":"B35","doi-asserted-by":"publisher","first-page":"2354","DOI":"10.1182\/blood.V128.22.2354.2354","article-title":"Comparison of survival and costs of rituximab-based chemotherapy for initial therapy of follicular lymphoma in elderly patients","volume":"128","author":"Shah","year":"2016","journal-title":"Blood"},{"key":"B36","doi-asserted-by":"publisher","first-page":"8023","DOI":"10.1200\/jco.2016.34.15_suppl.8023","article-title":"Can comorbidities predict survival of patients with multiple myeloma treated with autologous stem cell transplantation","volume":"34","author":"Veljanovska","year":"2016","journal-title":"J Clin Oncol"},{"key":"B37","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1093\/annonc\/mdp258","article-title":"Comorbidity as prognostic variable in MDS: comparative evaluation of the HCT-CI and CCI in a core dataset of 419 patients of the Austrian MDS Study Group","volume":"1","author":"Sperr","year":"2010","journal-title":"Annals Oncol"},{"key":"B38","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1182\/blood-2014-03-563759","article-title":"Carfilzomib, cyclophosphamide, and dexamethasone in patients with newly diagnosed multiple myeloma: a multicenter, phase 2 study","volume":"124","author":"Bringhen","year":"2014","journal-title":"Blood."},{"key":"B39","doi-asserted-by":"publisher","first-page":"1102","DOI":"10.1182\/blood-2015-08-662627","article-title":"Triplet vs doublet lenalidomide-containing regimens for the treatment of elderly patients with newly diagnosed multiple myeloma","volume":"127","author":"Magarotto","year":"2016","journal-title":"Blood."},{"key":"B40","doi-asserted-by":"publisher","first-page":"1110","DOI":"10.3324\/haematol.2016.148189","article-title":"Geriatric assessment in multiple myeloma patients: validation of the International Myeloma Working Group (IMWG) Score and Comparison with other Common Comorbidity Scores","volume":"101","author":"Engelhardt","year":"2016","journal-title":"Haematologica"},{"key":"B41","doi-asserted-by":"publisher","first-page":"4132","DOI":"10.1002\/cam4.1620","article-title":"Validation of multiple myeloma risk stratification indices in routine clinical practice: analysis of data from the Czech Myeloma Group Registry of Monoclonal Gammopathies","volume":"7","author":"Radocha","year":"2018","journal-title":"Cancer Med."},{"key":"B42","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1016\/j.jgo.2016.08.001","article-title":"Concise review - treatment of multiple myeloma in the very elderly: how do novel agents fit in?","volume":"7","author":"Kint","year":"2016","journal-title":"J Geriatr Oncol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1016\/j.clml.2012.06.008","article-title":"Assessment of vulnerability measures and their effect on survival in a real-life population of multiple myeloma patients registered at marche region multiple myeloma registry","volume":"12","author":"Offidani","year":"2012","journal-title":"Clin Lymphoma Myeloma Leukemia."},{"key":"B44","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1016\/j.clml.2013.03.013","article-title":"Validation of the Freiburg comorbidity index in 466 multiple myeloma patients and combination with the International Staging System are Highly Predictive for Outcome","volume":"13","author":"Kleber","year":"2013","journal-title":"Clin Lymphoma Myeloma Leukemia."},{"key":"B45","doi-asserted-by":"publisher","first-page":"910","DOI":"10.3324\/haematol.2016.162693","article-title":"A concise revised myeloma comorbidity index as a valid prognostic instrument in a large cohort of 801 multiple myeloma patients","volume":"102","author":"Engelhardt","year":"2017","journal-title":"Haematologica"},{"key":"B46","doi-asserted-by":"publisher","first-page":"e117","DOI":"10.1016\/S2352-3026(19)30011-0","article-title":"Frailty in multiple myeloma: the need for harmony to prevent doing harm","volume":"6","author":"Zweegman","year":"2019","journal-title":"Lancet Haematol."},{"key":"B47","doi-asserted-by":"publisher","first-page":"478","DOI":"10.1182\/asheducation-2013.1.478","article-title":"Monoclonal gammopathy of undetermined significance and smoldering multiple myeloma: biological insights and early treatment strategies","volume":"2013","author":"Landgren","year":"2013","journal-title":"Hematol Am Soc Hematol Educ Program."},{"key":"B48","doi-asserted-by":"publisher","first-page":"3380","DOI":"10.1182\/blood-2014-08-551549","article-title":"How I treat smoldering multiple myeloma","volume":"124","author":"Ghobrial","year":"2014","journal-title":"Blood."},{"key":"B49","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1111\/j.1365-2141.2011.08573.x","article-title":"Guidelines for the diagnosis and management of multiple myeloma 2011: guideline","volume":"154","author":"Bird","year":"2011","journal-title":"Brit J Haematol."},{"key":"B50","doi-asserted-by":"publisher","first-page":"1203","DOI":"10.1016\/j.bbmt.2017.03.012","article-title":"In-hospital mortality and post-transplantation complications in elderly multiple myeloma patients undergoing autologous hematopoietic stem cell transplantation: a population-based study","volume":"23","author":"Sanchez","year":"2017","journal-title":"Biol Blood Marrow Transpl."},{"key":"B51","doi-asserted-by":"publisher","first-page":"8956","DOI":"10.4081\/hr.2020.8956","article-title":"How I manage frontline transplant-ineligible multiple myeloma","volume":"12","author":"Derudas","year":"2020","journal-title":"Hematol Rep."},{"key":"B52","doi-asserted-by":"publisher","first-page":"448","DOI":"10.1200\/JCO.2012.41.6180","article-title":"Persistent overall survival benefit and no increased risk of second malignancies with bortezomib-melphalan-prednisone versus melphalan-prednisone in patients with previously untreated multiple myeloma","volume":"31","author":"San Miguel","year":"2013","journal-title":"JCO."},{"key":"B53","doi-asserted-by":"publisher","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":"B54","doi-asserted-by":"publisher","first-page":"470","DOI":"10.1111\/bjh.16095","article-title":"Frontline treatment of elderly non transplant-eligible multiple myeloma patients using cybord with or without thalidomide-based consolidation: a retrospective multi-centre analysis of real-world data","volume":"187","author":"Chan","year":"2019","journal-title":"Br J Haematol."},{"key":"B55","doi-asserted-by":"publisher","first-page":"480","DOI":"10.1016\/j.clml.2020.02.018","article-title":"Comparative efficacy of bortezomib, melphalan, and prednisone (VMP) with or without daratumumab versus VMP Alone in the treatment of newly diagnosed multiple myeloma: propensity score matching of ALCYONE and VISTA Phase III studies","volume":"20","author":"Cavo","year":"2020","journal-title":"Clin Lymphoma Myeloma Leukemia."},{"key":"B56","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1016\/S1470-2045(11)70081-X","article-title":"Subcutaneous versus intravenous administration of bortezomib in patients with relapsed multiple myeloma: a randomised, phase 3, non-inferiority study","volume":"12","author":"Moreau","year":"2011","journal-title":"Lancet Oncol."},{"key":"B57","doi-asserted-by":"publisher","first-page":"934","DOI":"10.1016\/S1470-2045(10)70187-X","article-title":"Bortezomib, melphalan, and prednisone versus bortezomib, thalidomide, and prednisone as induction therapy followed by maintenance treatment with bortezomib and thalidomide versus bortezomib and prednisone in elderly patients with untreated multiple myeloma: a randomised trial","volume":"11","author":"Mateos","year":"2010","journal-title":"Lancet Oncol."},{"key":"B58","doi-asserted-by":"publisher","first-page":"825","DOI":"10.1016\/S0140-6736(06)68338-4","article-title":"Oral melphalan and prednisone chemotherapy plus thalidomide compared with melphalan and prednisone alone in elderly patients with multiple myeloma: randomised controlled trial","volume":"367","author":"Palumbo","year":"2006","journal-title":"Lancet."},{"key":"B59","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1111\/j.1600-0609.2010.01524.x","article-title":"Addition of thalidomide to oral melphalan\/prednisone in patients with multiple myeloma not eligible for transplantation: results of a randomized trial from the Turkish myeloma study group: addition of thalidomide to oral melphalan\/prednisone in patients with multiple myeloma","volume":"86","author":"Beksac","year":"2011","journal-title":"Eur J Haematol."},{"key":"B60","doi-asserted-by":"publisher","first-page":"1209","DOI":"10.1016\/S0140-6736(07)61537-2","article-title":"Melphalan and prednisone plus thalidomide versus melphalan and prednisone alone or reduced-intensity autologous stem cell transplantation in elderly patients with multiple myeloma (IFM 99\u201306): a randomised trial","volume":"370","author":"Facon","year":"2007","journal-title":"Lancet."},{"key":"B61","doi-asserted-by":"publisher","first-page":"3160","DOI":"10.1200\/JCO.2009.26.1610","article-title":"Phase III study of the value of thalidomide added to melphalan plus prednisone in elderly patients with newly diagnosed multiple myeloma: the HOVON 49 Study","volume":"28","author":"Wijermans","year":"2010","journal-title":"JCO."},{"key":"B62","doi-asserted-by":"publisher","first-page":"1405","DOI":"10.1182\/blood-2009-08-237974","article-title":"Melphalan and prednisone plus thalidomide or placebo in elderly patients with multiple myeloma","volume":"116","author":"Waage","year":"2010","journal-title":"Blood."},{"key":"B63","doi-asserted-by":"publisher","first-page":"3664","DOI":"10.1200\/JCO.2008.21.0948","article-title":"Efficacy of Melphalan and prednisone plus thalidomide in patients older than 75 years with newly diagnosed multiple myeloma: IFM 01\/01 trial","volume":"27","author":"Hulin","year":"2009","journal-title":"JCO."},{"key":"B64","doi-asserted-by":"publisher","first-page":"689","DOI":"10.1038\/leu.2010.313","article-title":"Melphalan and prednisone versus melphalan, prednisone and thalidomide for elderly and\/or transplant ineligible patients with multiple myeloma: a meta-analysis","volume":"25","author":"Kapoor","year":"2011","journal-title":"Leukemia."},{"key":"B65","doi-asserted-by":"publisher","first-page":"1239","DOI":"10.1182\/blood-2011-03-341669","article-title":"Thalidomide for previously untreated elderly patients with multiple myeloma: meta-analysis of 1685. Individual patient data from 6 randomized clinical trials","volume":"118","author":"Fayers","year":"2011","journal-title":"Blood."},{"key":"B66","first-page":"543","article-title":"Review of thalidomide in the treatment of newly diagnosed multiple myeloma","volume":"3","author":"Cavallo","year":"2007","journal-title":"Ther Clin Risk Manag"},{"key":"B67","doi-asserted-by":"publisher","first-page":"1759","DOI":"10.1056\/NEJMoa1112704","article-title":"Continuous lenalidomide treatment for newly diagnosed multiple myeloma","volume":"366","author":"Palumbo","year":"2012","journal-title":"N Engl J Med."},{"key":"B68","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1007\/s40266-015-0269-6","article-title":"Lenalidomide: a review of its continuous use in patients with newly diagnosed multiple myeloma not eligible for stem-cell transplantation","volume":"32","author":"McCormack","year":"2015","journal-title":"Drugs Aging."},{"key":"B69","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/S1470-2045(09)70284-0","article-title":"Lenalidomide plus high-dose dexamethasone versus lenalidomide plus low-dose dexamethasone as initial therapy for newly diagnosed multiple myeloma: an open-label randomised controlled trial","volume":"11","author":"Rajkumar","year":"2010","journal-title":"Lancet Oncol."},{"key":"B70","doi-asserted-by":"publisher","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":"B71","doi-asserted-by":"publisher","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":"Haematol Supplement."},{"key":"B72","doi-asserted-by":"publisher","first-page":"3178","DOI":"10.1182\/blood-2019-128000","article-title":"Updated Results of a Phase 2 Study of Modified Lenalidomide, Bortezomib, and Dexamethasone (RVd-lite) in Transplant-Ineligible Multiple Myeloma","volume":"134","author":"O'Donnell","year":"2019","journal-title":"Blood."},{"key":"B73","doi-asserted-by":"publisher","first-page":"293","DOI":"10.3892\/mco.2018.1775","article-title":"Tolerability and safety of real-world use of pomalidomide in patients with relapsed\/refractory multiple myeloma","volume":"10","author":"Usami","year":"2019","journal-title":"Mol Clin Oncol."},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.25726","article-title":"Pomalidomide, cyclophosphamide, and dexamethasone for elderly patients with relapsed and refractory multiple myeloma: a study of the Korean Multiple Myeloma Working Party (KMMWP-164 Study)","author":"Lee","year":"2020","journal-title":"Am J Hematol."},{"key":"B75","doi-asserted-by":"publisher","first-page":"468","DOI":"10.3324\/haematol.2019.217448","article-title":"Daratumumab-based regimens are highly effective and well tolerated in relapsed or refractory multiple myeloma regardless of patient age: subgroup analysis of the phase 3 CASTOR and POLLUX studies","volume":"105","author":"Mateos","year":"2020"},{"key":"B76","doi-asserted-by":"publisher","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":"B77","doi-asserted-by":"publisher","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":"B78","doi-asserted-by":"publisher","first-page":"LBA-2","DOI":"10.1182\/blood-2018-120737","article-title":"Phase 3 randomized study of daratumumab plus lenalidomide and Dexamethasone (D-Rd) Versus Lenalidomide and Dexamethasone (Rd) in Patients with Newly Diagnosed Multiple Myeloma (NDMM) Ineligible for Transplant (MAIA)","volume":"132","author":"Facon","year":"2018","journal-title":"Blood."},{"key":"B79","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/S0140-6736(19)31240-1","article-title":"Bortezomib, thalidomide, and dexamethasone with or without daratumumab before and after autologous stem-cell transplantation for newly diagnosed multiple myeloma (CASSIOPEIA): a randomised, open-label, phase 3 study","volume":"394","author":"Moreau","year":"2019","journal-title":"Lancet."},{"key":"B80","doi-asserted-by":"publisher","first-page":"936","DOI":"10.1182\/blood.2020005288","article-title":"Daratumumab, lenalidomide, bortezomib, and dexamethasone for transplant-eligible newly diagnosed multiple myeloma: the GRIFFIN Trial","volume":"136","author":"Voorhees","year":"2020","journal-title":"Blood."},{"key":"B81","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1038\/s41408-020-00348-5","article-title":"Cytogenetic abnormalities in multiple myeloma: association with disease characteristics and treatment response","volume":"10","author":"Abdallah","year":"2020","journal-title":"Blood Cancer J."},{"key":"B82","doi-asserted-by":"publisher","first-page":"548","DOI":"10.1002\/ajh.25791","article-title":"Multiple myeloma: 2020 update on diagnosis, risk-stratification and management","volume":"95","author":"Rajkumar","year":"2020","journal-title":"Am J Hematol."},{"key":"B83","doi-asserted-by":"publisher","first-page":"604","DOI":"10.1038\/s41375-019-0595-5","article-title":"The relative importance of factors predicting outcome for myeloma patients at different ages: results from 3894 patients in the myeloma XI trial","volume":"34","author":"Pawlyn","year":"2020","journal-title":"Leukemia."},{"key":"B84","doi-asserted-by":"publisher","first-page":"243428","DOI":"10.3324\/haematol.2019.243428","article-title":"Carfilzomib, cyclophosphamide and dexamethasone for newly diagnosed, high-risk myeloma patients not eligible for transplant: a pooled analysis of two studies","volume":"2019","author":"Mina","year":"2020","journal-title":"Haematologica"},{"key":"B85","doi-asserted-by":"publisher","first-page":"2127","DOI":"10.1038\/s41375-019-0517-6","article-title":"Carfilzomib with immunomodulatory drugs for the treatment of newly diagnosed multiple myeloma","volume":"33","author":"Landgren","year":"2019","journal-title":"Leukemia."},{"key":"B86","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1186\/s13045-020-00948-5","article-title":"Daratumumab, bortezomib, and dexamethasone in relapsed or refractory multiple myeloma: subgroup analysis of CASTOR based on cytogenetic risk","volume":"13","author":"Weisel","year":"2020","journal-title":"J Hematol Oncol."},{"key":"B87","doi-asserted-by":"publisher","first-page":"e22888","DOI":"10.1002\/jcla.22888","article-title":"Clinical features and treatment outcome of elderly multiple myeloma patients with impaired renal function","volume":"33","author":"Chen","year":"2019","journal-title":"J Clin Lab Anal."},{"key":"B88","doi-asserted-by":"publisher","first-page":"1819","DOI":"10.3390\/cancers11111819","article-title":"Reactivation of hepatitis B virus in patients with multiple myeloma","volume":"11","author":"Tsukune","year":"2019","journal-title":"Cancers."},{"key":"B89","doi-asserted-by":"publisher","first-page":"1243","DOI":"10.11406\/rinketsu.60.1243","article-title":"Current management and emerging treatment strategies for multiple myeloma","volume":"60","author":"Lei","year":"2019","journal-title":"Rinsho Ketsueki."},{"key":"B90","doi-asserted-by":"publisher","first-page":"619","DOI":"10.2147\/CIA.S196087","article-title":"Updated perspectives on the management of multiple myeloma in older patients: focus on lenalidomide","volume":"15","author":"Schoenbeck","year":"2020","journal-title":"CIA."},{"key":"B91","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1200\/JOP.19.00244","article-title":"Current treatment strategies for multiple myeloma","volume":"16","author":"Branagan","year":"2020","journal-title":"JCO Oncology Pract."},{"key":"B92","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1016\/S1470-2045(18)30764-2","article-title":"Lenalidomide as maintenance for every newly diagnosed patient with multiple myeloma","volume":"20","author":"Mateos","year":"2019","journal-title":"Lancet Oncol"},{"key":"B93","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1016\/S0140-6736(18)33003-4","article-title":"Oral ixazomib maintenance following autologous stem cell transplantation (TOURMALINE-MM3): a double-blind, randomised, placebo-controlled phase 3 trial","volume":"393","author":"Dimopoulos","year":"2019","journal-title":"Lancet."},{"key":"B94","doi-asserted-by":"publisher","first-page":"2284","DOI":"10.1182\/blood-2015-05-643320","article-title":"Carfilzomib, pomalidomide, and dexamethasone for relapsed or refractory myeloma","volume":"126","author":"Shah","year":"2015","journal-title":"Blood."},{"key":"B95","doi-asserted-by":"publisher","first-page":"1198","DOI":"10.1182\/blood-2017-05-782961","article-title":"Pomalidomide, bortezomib, and dexamethasone for patients with relapsed lenalidomide-refractory multiple myeloma","volume":"130","author":"Paludo","year":"2017","journal-title":"Blood."},{"key":"B96","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1186\/s13045-018-0583-7","article-title":"Response and progression-free survival according to planned treatment duration in patients with relapsed multiple myeloma treated with carfilzomib, lenalidomide and dexamethasone (Krd) Versus Lenalidomide and Dexamethasone (Rd) in the phase III ASPIRE study","volume":"11","author":"Dimopoulos","year":"2018","journal-title":"J Hematol Oncol."},{"key":"B97","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1080\/14656566.2016.1274973","article-title":"Pomalidomide in multiple myeloma","volume":"18","author":"Uccello","year":"2017","journal-title":"Expert Opin Pharmacother."},{"key":"B98","doi-asserted-by":"publisher","first-page":"1811","DOI":"10.1056\/NEJMoa1805762","article-title":"Elotuzumab plus pomalidomide and dexamethasone for multiple myeloma","volume":"379","author":"Dimopoulos","year":"2018","journal-title":"N Engl J Med."},{"key":"B99","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1016\/S0140-6736(20)30734-0","article-title":"Carfilzomib, dexamethasone and daratumumab versus carfilzomib and dexamethasone for patients with relapsed or refractory multiple myeloma (CANDOR): results from a randomised, multicentre, open-label, phase 3 study","volume":"396","author":"Dimopoulos","year":"2020","journal-title":"Lancet."},{"key":"B100","first-page":"216","article-title":"Chapter 9: Management of multiple myeloma in developing countries","volume-title":"Update on Multiple Myeloma","author":"Nwabuko","year":"2018"},{"key":"B101","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1007\/s11899-020-00570-9","article-title":"Supportive care in multiple myeloma","volume":"15","author":"Guzdar","year":"2020","journal-title":"Curr Hematol Malig Rep."},{"key":"B102","doi-asserted-by":"publisher","first-page":"22","DOI":"10.6004\/jnccn.2018.7079","article-title":"Use of bisphosphonates in elderly patients with newly diagnosed multiple myeloma","volume":"17","author":"Leng","year":"2019","journal-title":"J Natl Comprehens Cancer Netw."},{"key":"B103","doi-asserted-by":"publisher","first-page":"370","DOI":"10.1016\/S1470-2045(18)30072-X","article-title":"Denosumab versus zoledronic acid in bone disease treatment of newly diagnosed multiple myeloma: an international, double-blind, double-dummy, randomized, controlled, phase 3 study","volume":"19","author":"Raje","year":"2018","journal-title":"Lancet Oncol."},{"key":"B104","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1111\/j.1600-0609.1994.tb00190.x","article-title":"Renal function in newly diagnosed multiple myeloma - a demographic study of 1353 patients","volume":"53","author":"Knudsen","year":"2009","journal-title":"Eur J Haematol."},{"key":"B105","doi-asserted-by":"publisher","first-page":"2037","DOI":"10.3390\/cancers11122037","article-title":"Pain management in patients with multiple myeloma: an update","volume":"11","author":"Coluzzi","year":"2019","journal-title":"Cancers."},{"key":"B106","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1038\/leu.2016.186","article-title":"Impact of prior treatment on patients with relapsed multiple myeloma treated with carfilzomib and dexamethasone vs bortezomib and dexamethasone in the phase 3 ENDEAVOR study","volume":"31","author":"Moreau","year":"2017","journal-title":"Leukemia."},{"key":"B107","doi-asserted-by":"publisher","first-page":"1061","DOI":"10.1080\/13696998.2016.1194278","article-title":"Cost-effectiveness of adding carfilzomib to lenalidomide and dexamethasone in relapsed multiple myeloma arom a US perspective","volume":"19","author":"Jakubowiak","year":"2016","journal-title":"J Med Econ."},{"key":"B108","doi-asserted-by":"publisher","first-page":"893","DOI":"10.1182\/blood-2012-10-459883","article-title":"Carfilzomib","volume":"121","author":"Kortuem","year":"2013","journal-title":"Blood."},{"key":"B109","doi-asserted-by":"publisher","first-page":"3100","DOI":"10.1182\/blood-2015-02-626168","article-title":"Phase 1\/2 study of carfilzomib plus melphalan and prednisone in patients aged over 65 years with newly diagnosed multiple myeloma","volume":"125","author":"Moreau","year":"2015","journal-title":"Blood."},{"key":"B110","doi-asserted-by":"publisher","first-page":"4224","DOI":"10.1158\/1078-0432.CCR-18-3642","article-title":"Carfilzomib weekly plus melphalan and prednisone in newly diagnosed transplant-ineligible multiple myeloma (IFM 2012-03): a phase I trial","volume":"25","author":"Leleu","year":"2019","journal-title":"Clin Cancer Res."},{"key":"B111","doi-asserted-by":"publisher","first-page":"404","DOI":"10.1111\/bjh.14549","article-title":"Carfilzomib, lenalidomide, and dexamethasone in patients with relapsed multiple myeloma categorised by age: secondary analysis from the phase 3 ASPIRE study","volume":"177","author":"Dimopoulos","year":"2017","journal-title":"Br J Haematol."},{"key":"B112","first-page":"102","article-title":"Ninlaro (Ixazomib): First oral proteasome inhibitor approved for the treatment of patients with relapsed or refractory multiple myeloma","volume":"9","author":"Raedler","year":"2016","journal-title":"Am Health Drug Benefits."},{"key":"B113","doi-asserted-by":"publisher","first-page":"985","DOI":"10.1002\/ajh.25134","article-title":"Patient-reported health-related quality of life from the phase III TOURMALINE-MM1 study of ixazomib-lenalidomide-dexamethasone versus placebo-lenalidomide-dexamethasone in relapsed\/refractory multiple myeloma","volume":"93","author":"Leleu","year":"2018","journal-title":"Am J Hematol."},{"key":"B114","doi-asserted-by":"publisher","first-page":"1615","DOI":"10.1007\/s12253-019-00607-2","article-title":"Real world efficacy and safety results of ixazomib lenalidomide and dexamethasone combination in relapsed\/refractory multiple myeloma: data collected from the hungarian ixazomib named patient program","volume":"25","author":"Varga","year":"2019","journal-title":"Pathol Oncol Res."},{"key":"B115","doi-asserted-by":"publisher","first-page":"332","DOI":"10.1182\/blood.V120.21.332.332","article-title":"A Phase 1\/2 study of weekly MLN9708, an investigational oral proteasome inhibitor, in combination with lenalidomide and dexamethasone in patients with previously untreated multiple myeloma (MM)","volume":"120","author":"Kumar","year":"2012","journal-title":"Blood."},{"key":"B116","doi-asserted-by":"publisher","first-page":"e338","DOI":"10.1038\/bcj.2015.60","article-title":"Phase 2 trial of ixazomib in patients with relapsed multiple myeloma not refractory to bortezomib","volume":"4","author":"Kumar","year":"2015","journal-title":"Blood Cancer J."},{"key":"B117","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1016\/j.htct.2018.07.003","article-title":"New proteasome inhibitors in the treatment of multiple myeloma","volume":"41","author":"Hungria","year":"2019","journal-title":"Hematol Transfusion Cell Therapy."},{"key":"B118","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1186\/s13045-016-0284-z","article-title":"Elotuzumab for the treatment of multiple myeloma","volume":"9","author":"Wang","year":"2016","journal-title":"J Hematol Oncol."},{"key":"B119","doi-asserted-by":"publisher","first-page":"552","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":"B120","doi-asserted-by":"publisher","first-page":"1953","DOI":"10.1200\/JCO.2011.37.2649","article-title":"Elotuzumab in combination with lenalidomide and low-dose dexamethasone in relapsed or refractory multiple myeloma","volume":"30","author":"Lonial","year":"2012","journal-title":"JCO."},{"key":"B121","doi-asserted-by":"publisher","first-page":"e516","DOI":"10.1016\/S2352-3026(15)00197-0","article-title":"Elotuzumab in combination with lenalidomide and dexamethasone in patients with relapsed multiple myeloma: final phase 2 results from the randomised, open-label, phase 1b\u22122 dose-escalation study","volume":"2","author":"Richardson","year":"2015","journal-title":"Lancet Haematol."},{"key":"B122","doi-asserted-by":"publisher","first-page":"896","DOI":"10.1111\/bjh.14787","article-title":"Elotuzumab plus lenalidomide\/dexamethasone for relapsed or refractory multiple myeloma: ELOQUENT-2 follow-up and post-hoc analyses on progression-free survival and tumour growth","volume":"178","author":"Dimopoulos","year":"2017","journal-title":"Br J Haematol."},{"key":"B123","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1007\/s12185-019-02757-0","article-title":"Elotuzumab plus lenalidomide and dexamethasone for newly diagnosed multiple myeloma: a randomized, open-label, phase 2 study in Japan","volume":"111","author":"Kubo","year":"2020","journal-title":"Int J Hematol."},{"key":"B124","doi-asserted-by":"publisher","first-page":"1228","DOI":"10.3389\/fimmu.2018.01228","article-title":"Daratumumab for the Treatment of Multiple Myeloma","volume":"9","author":"Plesner","year":"2018","journal-title":"Front Immunol."},{"key":"B125","doi-asserted-by":"publisher","first-page":"1264","DOI":"10.1056\/NEJMe1509419","article-title":"Monoclonal antibodies in multiple myeloma come of age","volume":"373","author":"Raje","year":"2015","journal-title":"N Engl J Med."},{"key":"B126","doi-asserted-by":"publisher","first-page":"1207","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":"B127","doi-asserted-by":"publisher","first-page":"1319","DOI":"10.1056\/NEJMoa1607751","article-title":"Daratumumab, lenalidomide, and dexamethasone for multiple myeloma","volume":"375","author":"Dimopoulos","year":"2016","journal-title":"N Engl J Med."},{"key":"B128","doi-asserted-by":"publisher","first-page":"754","DOI":"10.1056\/NEJMoa1606038","article-title":"Daratumumab, bortezomib, and dexamethasone for multiple myeloma","volume":"375","author":"Palumbo","year":"2016","journal-title":"N Engl J Med."},{"key":"B129","doi-asserted-by":"publisher","first-page":"2172","DOI":"10.1056\/NEJMe1904372","article-title":"Initial therapy in older patients with multiple myeloma","volume":"380","author":"Laubach","year":"2019","journal-title":"N Engl J Med."}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2021.612696\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,2,25]],"date-time":"2021-02-25T07:30:39Z","timestamp":1614238239000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2021.612696\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,25]]},"references-count":129,"alternative-id":["10.3389\/fmed.2021.612696"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2021.612696","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,25]]},"article-number":"612696"}}