Prognostic Impact of Serum Free Light Chain Ratio Normalization in Patients with Multiple Myeloma Treated within the GMMG-MM5 Trial
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 t...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-09-01
|
| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/13/19/4856 |
| _version_ | 1797516702830821376 |
|---|---|
| author | Eva-Maria Klein Diana Tichy Hans J. Salwender Elias K. Mai Jan Duerig Katja C. Weisel Axel Benner Uta Bertsch Mabast Akhavanpoor Britta Besemer Markus Munder Hans-Walter Lindemann Dirk Hose Anja Seckinger Steffen Luntz Anna Jauch Ahmet Elmaagacli Stephan Fuhrmann Peter Brossart Martin Goerner Helga Bernhard Marc S. Raab Igor W. Blau Mathias Haenel Christof Scheid Hartmut Goldschmidt on behalf of the German-Speaking Myeloma Multicenter Group (GMMG) |
| author_facet | Eva-Maria Klein Diana Tichy Hans J. Salwender Elias K. Mai Jan Duerig Katja C. Weisel Axel Benner Uta Bertsch Mabast Akhavanpoor Britta Besemer Markus Munder Hans-Walter Lindemann Dirk Hose Anja Seckinger Steffen Luntz Anna Jauch Ahmet Elmaagacli Stephan Fuhrmann Peter Brossart Martin Goerner Helga Bernhard Marc S. Raab Igor W. Blau Mathias Haenel Christof Scheid Hartmut Goldschmidt on behalf of the German-Speaking Myeloma Multicenter Group (GMMG) |
| author_sort | Eva-Maria Klein |
| collection | DOAJ |
| description | 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) (<i>p</i> < 0.01, hazard ratio (HR) = 0.61, 95% confidence interval (95% CI) = 0.47–0.79) and overall survival (OS) (<i>p</i> = 0.02, HR = 0.67, 95% CI = 0.48–0.93) 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 (<i>p</i> = 0.04, HR = 0.77, 95% CI = 0.60–0.99) and OS (<i>p</i> = 0.01, HR = 0.59, 95% CI = 0.41–0.86). 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. |
| first_indexed | 2024-03-10T07:04:33Z |
| format | Article |
| id | doaj.art-2bd4474252bd46afbfd0c00fb6855c0f |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T07:04:33Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-2bd4474252bd46afbfd0c00fb6855c0f2023-11-22T15:53:26ZengMDPI AGCancers2072-66942021-09-011319485610.3390/cancers13194856Prognostic Impact of Serum Free Light Chain Ratio Normalization in Patients with Multiple Myeloma Treated within the GMMG-MM5 TrialEva-Maria Klein0Diana Tichy1Hans J. Salwender2Elias K. Mai3Jan Duerig4Katja C. Weisel5Axel Benner6Uta Bertsch7Mabast Akhavanpoor8Britta Besemer9Markus Munder10Hans-Walter Lindemann11Dirk Hose12Anja Seckinger13Steffen Luntz14Anna Jauch15Ahmet Elmaagacli16Stephan Fuhrmann17Peter Brossart18Martin Goerner19Helga Bernhard20Marc S. Raab21Igor W. Blau22Mathias Haenel23Christof Scheid24Hartmut Goldschmidt25on behalf of the German-Speaking Myeloma Multicenter Group (GMMG)Department of Medicine V, Hematology, Oncology and Rheumatology, University of Heidelberg, 69120 Heidelberg, GermanyDivision of Biostatistics, German Cancer Research Center (DKFZ), 69120 Heidelberg, GermanyAsklepios Tumorzentrum Hamburg, AK Altona and AK St. Georg, 22763 Hamburg, GermanyDepartment of Medicine V, Hematology, Oncology and Rheumatology, University of Heidelberg, 69120 Heidelberg, GermanyDepartment of Hematology, University Clinic Essen, 45147 Essen, GermanyDepartment of Oncology, Hematology and Bone Marrow Transplantation with Section of Pneumology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, GermanyDivision of Biostatistics, German Cancer Research Center (DKFZ), 69120 Heidelberg, GermanyDepartment of Medicine V, Hematology, Oncology and Rheumatology, University of Heidelberg, 69120 Heidelberg, GermanyDepartment of Medicine V, Hematology, Oncology and Rheumatology, University of Heidelberg, 69120 Heidelberg, GermanyDepartment of Hematology, Oncology and Immunology, University Hospital Tübingen, 72076 Tübingen, GermanyDepartment of Internal Medicine III, University Medical Center Mainz, 55131 Mainz, GermanyDepartment of Hematology and Oncology, Katholisches Krankenhaus Hagen, 58097 Hagen, GermanyDepartment of Medicine V, Hematology, Oncology and Rheumatology, University of Heidelberg, 69120 Heidelberg, GermanyDepartment of Medicine V, Hematology, Oncology and Rheumatology, University of Heidelberg, 69120 Heidelberg, GermanyCoordination Centre for Clinical Trials (KKS) Heidelberg, 69120 Heidelberg, GermanyInstitute of Human Genetics, University of Heidelberg, 69120 Heidelberg, GermanyDepartment of Hematology and Oncology, Asklepios Hospital Hamburg St. Georg, 20099 Hamburg, GermanyDepartment of Hematology and Oncology, Helios Hospital Berlin Buch, 13125 Berlin, GermanyDepartment of Internal Medicine, Oncology, Hematology, Immuno-Oncology and Rheumatology/Clinical Immunology, University Hospital Bonn, 53127 Bonn, GermanyDepartment of Hematology, Oncology and Palliative Care, Klinikum Bielefeld, 33604 Bielefeld, GermanyInternal Medicine V, Klinikum Darmstadt, 64283 Darmstadt, GermanyDepartment of Medicine V, Hematology, Oncology and Rheumatology, University of Heidelberg, 69120 Heidelberg, GermanyMedical Clinic, Charité University Medicine Berlin, 13353 Berlin, GermanyDepartment of Internal Medicine III, Klinikum Chemnitz, 09116 Chemnitz, GermanyDepartment of Internal Medicine I, University Hospital Cologne, 50937 Cologne, GermanyDepartment of Medicine V, Hematology, Oncology and Rheumatology, University of Heidelberg, 69120 Heidelberg, GermanyWe 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) (<i>p</i> < 0.01, hazard ratio (HR) = 0.61, 95% confidence interval (95% CI) = 0.47–0.79) and overall survival (OS) (<i>p</i> = 0.02, HR = 0.67, 95% CI = 0.48–0.93) 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 (<i>p</i> = 0.04, HR = 0.77, 95% CI = 0.60–0.99) and OS (<i>p</i> = 0.01, HR = 0.59, 95% CI = 0.41–0.86). 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.https://www.mdpi.com/2072-6694/13/19/4856multiple myelomaprognostic factorsserum free light chain ratio normalizationimmune reconstitutiontime-dependent analysis |
| spellingShingle | Eva-Maria Klein Diana Tichy Hans J. Salwender Elias K. Mai Jan Duerig Katja C. Weisel Axel Benner Uta Bertsch Mabast Akhavanpoor Britta Besemer Markus Munder Hans-Walter Lindemann Dirk Hose Anja Seckinger Steffen Luntz Anna Jauch Ahmet Elmaagacli Stephan Fuhrmann Peter Brossart Martin Goerner Helga Bernhard Marc S. Raab Igor W. Blau Mathias Haenel Christof Scheid Hartmut Goldschmidt on behalf of the German-Speaking Myeloma Multicenter Group (GMMG) Prognostic Impact of Serum Free Light Chain Ratio Normalization in Patients with Multiple Myeloma Treated within the GMMG-MM5 Trial Cancers multiple myeloma prognostic factors serum free light chain ratio normalization immune reconstitution time-dependent analysis |
| title | Prognostic Impact of Serum Free Light Chain Ratio Normalization in Patients with Multiple Myeloma Treated within the GMMG-MM5 Trial |
| title_full | Prognostic Impact of Serum Free Light Chain Ratio Normalization in Patients with Multiple Myeloma Treated within the GMMG-MM5 Trial |
| title_fullStr | Prognostic Impact of Serum Free Light Chain Ratio Normalization in Patients with Multiple Myeloma Treated within the GMMG-MM5 Trial |
| title_full_unstemmed | Prognostic Impact of Serum Free Light Chain Ratio Normalization in Patients with Multiple Myeloma Treated within the GMMG-MM5 Trial |
| title_short | Prognostic Impact of Serum Free Light Chain Ratio Normalization in Patients with Multiple Myeloma Treated within the GMMG-MM5 Trial |
| title_sort | prognostic impact of serum free light chain ratio normalization in patients with multiple myeloma treated within the gmmg mm5 trial |
| topic | multiple myeloma prognostic factors serum free light chain ratio normalization immune reconstitution time-dependent analysis |
| url | https://www.mdpi.com/2072-6694/13/19/4856 |
| work_keys_str_mv | AT evamariaklein prognosticimpactofserumfreelightchainrationormalizationinpatientswithmultiplemyelomatreatedwithinthegmmgmm5trial AT dianatichy prognosticimpactofserumfreelightchainrationormalizationinpatientswithmultiplemyelomatreatedwithinthegmmgmm5trial AT hansjsalwender prognosticimpactofserumfreelightchainrationormalizationinpatientswithmultiplemyelomatreatedwithinthegmmgmm5trial AT eliaskmai prognosticimpactofserumfreelightchainrationormalizationinpatientswithmultiplemyelomatreatedwithinthegmmgmm5trial AT janduerig prognosticimpactofserumfreelightchainrationormalizationinpatientswithmultiplemyelomatreatedwithinthegmmgmm5trial AT katjacweisel prognosticimpactofserumfreelightchainrationormalizationinpatientswithmultiplemyelomatreatedwithinthegmmgmm5trial AT axelbenner prognosticimpactofserumfreelightchainrationormalizationinpatientswithmultiplemyelomatreatedwithinthegmmgmm5trial AT utabertsch prognosticimpactofserumfreelightchainrationormalizationinpatientswithmultiplemyelomatreatedwithinthegmmgmm5trial AT mabastakhavanpoor prognosticimpactofserumfreelightchainrationormalizationinpatientswithmultiplemyelomatreatedwithinthegmmgmm5trial AT brittabesemer prognosticimpactofserumfreelightchainrationormalizationinpatientswithmultiplemyelomatreatedwithinthegmmgmm5trial AT markusmunder prognosticimpactofserumfreelightchainrationormalizationinpatientswithmultiplemyelomatreatedwithinthegmmgmm5trial AT hanswalterlindemann prognosticimpactofserumfreelightchainrationormalizationinpatientswithmultiplemyelomatreatedwithinthegmmgmm5trial AT dirkhose prognosticimpactofserumfreelightchainrationormalizationinpatientswithmultiplemyelomatreatedwithinthegmmgmm5trial AT anjaseckinger prognosticimpactofserumfreelightchainrationormalizationinpatientswithmultiplemyelomatreatedwithinthegmmgmm5trial AT steffenluntz prognosticimpactofserumfreelightchainrationormalizationinpatientswithmultiplemyelomatreatedwithinthegmmgmm5trial AT annajauch prognosticimpactofserumfreelightchainrationormalizationinpatientswithmultiplemyelomatreatedwithinthegmmgmm5trial AT ahmetelmaagacli prognosticimpactofserumfreelightchainrationormalizationinpatientswithmultiplemyelomatreatedwithinthegmmgmm5trial AT stephanfuhrmann prognosticimpactofserumfreelightchainrationormalizationinpatientswithmultiplemyelomatreatedwithinthegmmgmm5trial AT peterbrossart prognosticimpactofserumfreelightchainrationormalizationinpatientswithmultiplemyelomatreatedwithinthegmmgmm5trial AT martingoerner prognosticimpactofserumfreelightchainrationormalizationinpatientswithmultiplemyelomatreatedwithinthegmmgmm5trial AT helgabernhard prognosticimpactofserumfreelightchainrationormalizationinpatientswithmultiplemyelomatreatedwithinthegmmgmm5trial AT marcsraab prognosticimpactofserumfreelightchainrationormalizationinpatientswithmultiplemyelomatreatedwithinthegmmgmm5trial AT igorwblau prognosticimpactofserumfreelightchainrationormalizationinpatientswithmultiplemyelomatreatedwithinthegmmgmm5trial AT mathiashaenel prognosticimpactofserumfreelightchainrationormalizationinpatientswithmultiplemyelomatreatedwithinthegmmgmm5trial AT christofscheid prognosticimpactofserumfreelightchainrationormalizationinpatientswithmultiplemyelomatreatedwithinthegmmgmm5trial AT hartmutgoldschmidt prognosticimpactofserumfreelightchainrationormalizationinpatientswithmultiplemyelomatreatedwithinthegmmgmm5trial AT onbehalfofthegermanspeakingmyelomamulticentergroupgmmg prognosticimpactofserumfreelightchainrationormalizationinpatientswithmultiplemyelomatreatedwithinthegmmgmm5trial |