{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T05:43:16Z","timestamp":1788414196848,"version":"build-2803163510"},"reference-count":42,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2021,9,28]],"date-time":"2021-09-28T00:00:00Z","timestamp":1632787200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006436","name":"Celgene","doi-asserted-by":"publisher","award":["follows"],"award-info":[{"award-number":["follows"]}],"id":[{"id":"10.13039\/100006436","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010795","name":"Chugai Pharmaceutical","doi-asserted-by":"publisher","award":["follows"],"award-info":[{"award-number":["follows"]}],"id":[{"id":"10.13039\/100010795","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015756","name":"Janssen-Cilag","doi-asserted-by":"publisher","award":["follows"],"award-info":[{"award-number":["follows"]}],"id":[{"id":"10.13039\/100015756","id-type":"DOI","asserted-by":"publisher"}]},{"name":"The Binding Site","award":["follows"],"award-info":[{"award-number":["follows"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>We investigated the prognostic impact of time-dependent serum free light chain ratio (FLCr) normalization in 590 patients with secretory multiple myeloma (MM) during first-line treatment within the German-Speaking Myeloma Multicenter Group MM5 trial. Serum free light chains (sFLC) were assessed by the Freelite test at baseline, after induction, mobilization, autologous blood stem cell transplantation, consolidation and every three months during maintenance or follow up within two years after the start of maintenance. The proportion of patients with a normal or normalized FLCr increased from 3.6% at baseline to 23.2% after induction and 64.7% after consolidation. The achievement of FLCr normalization at any one time before the start of maintenance was associated with significantly prolonged progression-free survival (PFS) (p &lt; 0.01, hazard ratio (HR) = 0.61, 95% confidence interval (95% CI) = 0.47\u20130.79) and overall survival (OS) (p = 0.02, HR = 0.67, 95% CI = 0.48\u20130.93) in multivariable time-dependent Cox regression analyses. Furthermore, reaching immune reconstitution, defined as the normalization of uninvolved immunoglobulins, before maintenance was associated with superior PFS (p = 0.04, HR = 0.77, 95% CI = 0.60\u20130.99) and OS (p = 0.01, HR = 0.59, 95% CI = 0.41\u20130.86). We conclude that FLCr normalization during therapy is an important favorable prognostic factor in MM. Therefore, we recommend serial measurements of sFLC during therapy until achieving FLCr normalization, even in patients with secretory MM.<\/jats:p>","DOI":"10.3390\/cancers13194856","type":"journal-article","created":{"date-parts":[[2021,9,28]],"date-time":"2021-09-28T12:29:14Z","timestamp":1632832154000},"page":"4856","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Prognostic Impact of Serum Free Light Chain Ratio Normalization in Patients with Multiple Myeloma Treated within the GMMG-MM5 Trial"],"prefix":"10.3390","volume":"13","author":[{"given":"Eva-Maria","family":"Klein","sequence":"first","affiliation":[{"name":"Department of Medicine V, Hematology, Oncology and Rheumatology, University of Heidelberg, 69120 Heidelberg, Germany"},{"name":"Department of Internal Medicine 5, Klinikum Nuremberg, Paracelsus Medical University, 90419 Nuremberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Tichy","sequence":"additional","affiliation":[{"name":"Division of Biostatistics, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans","family":"Salwender","sequence":"additional","affiliation":[{"name":"Asklepios Tumorzentrum Hamburg, AK Altona and AK St. Georg, 22763 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6226-1252","authenticated-orcid":false,"given":"Elias","family":"Mai","sequence":"additional","affiliation":[{"name":"Department of Medicine V, Hematology, Oncology and Rheumatology, University of Heidelberg, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Duerig","sequence":"additional","affiliation":[{"name":"Department of Hematology, University Clinic Essen, 45147 Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katja","family":"Weisel","sequence":"additional","affiliation":[{"name":"Department of Oncology, Hematology and Bone Marrow Transplantation with Section of Pneumology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Axel","family":"Benner","sequence":"additional","affiliation":[{"name":"Division of Biostatistics, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uta","family":"Bertsch","sequence":"additional","affiliation":[{"name":"Department of Medicine V, Hematology, Oncology and Rheumatology, University of Heidelberg, 69120 Heidelberg, Germany"},{"name":"National Center for Tumor Diseases, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mabast","family":"Akhavanpoor","sequence":"additional","affiliation":[{"name":"Department of Medicine V, Hematology, Oncology and Rheumatology, University of Heidelberg, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Britta","family":"Besemer","sequence":"additional","affiliation":[{"name":"Department of Hematology, Oncology and Immunology, University Hospital T\u00fcbingen, 72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Munder","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine III, University Medical Center Mainz, 55131 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans-Walter","family":"Lindemann","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology, Katholisches Krankenhaus Hagen, 58097 Hagen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk","family":"Hose","sequence":"additional","affiliation":[{"name":"Department of Medicine V, Hematology, Oncology and Rheumatology, University of Heidelberg, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2771-712X","authenticated-orcid":false,"given":"Anja","family":"Seckinger","sequence":"additional","affiliation":[{"name":"Department of Medicine V, Hematology, Oncology and Rheumatology, University of Heidelberg, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steffen","family":"Luntz","sequence":"additional","affiliation":[{"name":"Coordination Centre for Clinical Trials (KKS) Heidelberg, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Jauch","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, University of Heidelberg, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmet","family":"Elmaagacli","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology, Asklepios Hospital Hamburg St. Georg, 20099 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7785-2565","authenticated-orcid":false,"given":"Stephan","family":"Fuhrmann","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology, Helios Hospital Berlin Buch, 13125 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Brossart","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Oncology, Hematology, Immuno-Oncology and Rheumatology\/Clinical Immunology, University Hospital Bonn, 53127 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Goerner","sequence":"additional","affiliation":[{"name":"Department of Hematology, Oncology and Palliative Care, Klinikum Bielefeld, 33604 Bielefeld, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helga","family":"Bernhard","sequence":"additional","affiliation":[{"name":"Internal Medicine V, Klinikum Darmstadt, 64283 Darmstadt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Raab","sequence":"additional","affiliation":[{"name":"Department of Medicine V, Hematology, Oncology and Rheumatology, University of Heidelberg, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Igor","family":"Blau","sequence":"additional","affiliation":[{"name":"Medical Clinic, Charit\u00e9 University Medicine Berlin, 13353 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathias","family":"Haenel","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine III, Klinikum Chemnitz, 09116 Chemnitz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christof","family":"Scheid","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I, University Hospital Cologne, 50937 Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0961-0035","authenticated-orcid":false,"given":"Hartmut","family":"Goldschmidt","sequence":"additional","affiliation":[{"name":"Department of Medicine V, Hematology, Oncology and Rheumatology, University of Heidelberg, 69120 Heidelberg, Germany"},{"name":"National Center for Tumor Diseases, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"on behalf of the German-Speaking Myeloma Multicenter Group 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