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@ARTICLE{Klein:177028,
      author       = {E.-M. Klein and D. Tichy$^*$ and H. J. Salwender and E. K.
                      Mai and J. Duerig and K. C. Weisel and A. Benner$^*$ and U.
                      Bertsch and M. Akhavanpoor and B. Besemer and M. Munder and
                      H.-W. Lindemann and D. Hose and A. Seckinger and S. Luntz
                      and A. Jauch and A. Elmaagacli and S. Fuhrmann and P.
                      Brossart and M. Goerner and H. Bernhard and M. S. Raab and
                      I. W. Blau and M. Haenel and C. Scheid and H. Goldschmidt
                      and On Behalf Of The German-Speaking Myeloma Multicenter
                      Group Gmmg},
      title        = {{P}rognostic {I}mpact of {S}erum {F}ree {L}ight {C}hain
                      {R}atio {N}ormalization in {P}atients with {M}ultiple
                      {M}yeloma {T}reated within the {GMMG}-{MM}5 {T}rial.},
      journal      = {Cancers},
      volume       = {13},
      number       = {19},
      issn         = {2072-6694},
      address      = {Basel},
      publisher    = {MDPI},
      reportid     = {DKFZ-2021-02258},
      pages        = {4856},
      year         = {2021},
      abstract     = {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 < 0.01, hazard
                      ratio (HR) = 0.61, $95\%$ confidence interval $(95\%$ CI) =
                      0.47-0.79) and overall survival (OS) (p = 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 (p = 0.04, HR = 0.77, $95\%$ CI = 0.60-0.99)
                      and OS (p = 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.},
      keywords     = {immune reconstitution (Other) / multiple myeloma (Other) /
                      prognostic factors (Other) / serum free light chain ratio
                      normalization (Other) / time-dependent analysis (Other)},
      cin          = {C060},
      ddc          = {610},
      cid          = {I:(DE-He78)C060-20160331},
      pnm          = {313 - Krebsrisikofaktoren und Prävention (POF4-313)},
      pid          = {G:(DE-HGF)POF4-313},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:34638344},
      doi          = {10.3390/cancers13194856},
      url          = {https://inrepo02.dkfz.de/record/177028},
}