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@ARTICLE{Richardson:305756,
      author       = {T. Richardson and E. Mai and E. Menis and A. Benner$^*$ and
                      D. Tichy$^*$ and K. Miah$^*$ and M. Hänel and B. Besemer
                      and A. Boquoi and I. W. Blau and C. S. Michel and H. W.
                      Lindemann and S. Janjetovic and P. Brossart and H. Bernhard
                      and P. Reimer and H. Salwender and D. Hose and A. Seckinger
                      and M. Raab and H. Goldschmidt and C. Scheid},
      collaboration = {G. M. M. Group},
      othercontributors = {K. F. K. Studien and K. Heidelberg and F. H. U. Onkologie
                          and P. H. Onkologie and F. Onkologie and C. K. B.
                          Mergentheim and M. Baden-Baden and C. U. Berlin and C. U.
                          Berlin and H. K. Berlin-Buch and M. Versorgungszentrum and
                          F. Onkologie and O. Seestrasse and K. B. Mitte and F.
                          Onkologie and U. Bonn and J. K. Bonn and O. Rheinsieg and S.
                          K. Braunschweig and O. Schwerpunktpraxis and O. P. I. K.
                          Buchholz and O. Schwerpunktpraxis and K. Chemnitz and R. K.
                          GmbH and C.-T.-K. Cottbus and K. Darmstadt and O.
                          Schwerpunktpraxis and G. F. H. U. Onkologie and F. F. H. U.
                          Onkologie and U. Essen and E. K. E. Z. F. I. Medizin and U.
                          Frankfurt and A. M. Versorgungszentrum and M. Frankfurt and
                          K. Nordwest and I. Facharztzentrum and I. Frankfurt and V.
                          GmbH and F. Rotkreuz-Kliniken and P. F. I. O. U.
                          Hämatologie and O. Facharztpraxis and F. F. H. U. Onkologie
                          and K. K. Hagen and A. K. Altona and A. K. St Georg and H.
                          P. Altona and F. F. H. U. Onkologie and O. L. Ug and E. K.
                          H. gGmbH and O. Schwerpunktpraxis and K. H. GmbH and K. R.
                          Hannover and O. A. O. Hannover and U. Heidelberg and O.
                          Schwerpunktpraxis and O. S. Heilbronn and S. K. H. GmbH and
                          F. F. H. U. Tumorerkrankungen and U. d. Saarlandes and K.
                          Idar-Oberstein and S. F. H. U. Onkologie and G. F.
                          Hämatologie and U. Köln and O. Köln and P. I. O. U.
                          Hämatologie and K. Köln and F. F. Hämatologie and O. Z.
                          Lebach and K. d. S. L. A. Rhein and O. S. Lüneburg and U.
                          der Johannes Gutenberg-Universität Mainz and M.
                          Facharztzentrum and U. Mannheim and M. O. Praxis and F. F.
                          I. Medizin and P. F. I. Medizin and A. J. W. K. Minden and
                          K. M. Hilf and S. K. München and F. F. I. Medizin and M.
                          Kliniken and O. Facharztpraxis and P. Kliniken and M.
                          Kliniken and M. V. A. S. S. Trudbert-Klinikum and O. P.
                          Pinneberg and G. I. Medizin/Onkologie and F. F. Onkologie
                          and D. S. Hall and Z. F. A. H. U. Onkologie and D. K.
                          Jung-Stilling and G. O. Bodensee and O. S. Speyer and M.
                          Stuttgart and K. der Barmherzigen Brüder Trier and K. M.
                          der Borromäerinnen Trier and O. S. A. B. Trier and O.
                          Rheinsieg and U. Tübingen and O. O. M. GmbH and F. F.
                          Onkologie and A. Klinik and F. F. Onkologie},
      title        = {{P}rognostic {I}mpact of the {H}evylite {A}ssay in
                      {P}atients {W}ith {I}g{G} or {I}g{A} {M}ultiple {M}yeloma
                      {T}reated {W}ithin the {GMMG}-{MM}5 {T}rial.},
      journal      = {European journal of haematology},
      volume       = {nn},
      issn         = {0902-4441},
      address      = {Oxford},
      publisher    = {Wiley-Blackwell},
      reportid     = {DKFZ-2025-02376},
      pages        = {nn},
      year         = {2025},
      note         = {epub},
      abstract     = {Response assessment during treatment of multiple myeloma
                      (MM) typically relies on immunofixation and serum
                      electrophoresis. However, low levels of IgG and especially
                      IgA paraprotein are difficult to quantify reliably. The
                      Hevylite Assay quantifies the kappa and lambda fractions of
                      IgG and IgA separately and is useful to determine response
                      to therapy. Using serum samples of 360 evaluable patients
                      from the prospective GMMG-MM5 trial (EudraCT-No.
                      2010-019173-16) we assessed the normalization of the
                      kappa/lambda ratio with the Hevylite Assay (HLCr) 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 end of consolidation. We observed a steady
                      increase in the proportion of patients with normalized HLCr
                      over the course of therapyAchieving HLCr normalization any
                      time until the end of consolidation was associated with a
                      trend towards a prolonged progression-free survival (PFS;
                      hazard ratio (HR) = 0.75, $95\%$ confidence interval $(95\%$
                      CI) = 0.56-1.01, p = 0.06) but not overall survival (OS; HR
                      = 0.94, $95\%$ CI = 0.69-1.26, p = 0.66) in multivariable
                      time-dependent Cox regression analyses. Using a landmark
                      analysis from the end of consolidation there was again a
                      marginally statistically significant effect of HLCr
                      normalization by the end of consolidation on PFS using a
                      multivariable Cox model on the subset of the two study arms
                      with continuous lenalidomide maintenance (HR 0.61, $95\%$ CI
                      0.37-1.02, p = 0.06). No such effect was observed in study
                      arms in which maintenance was only applied to patients not
                      in CR at the end of consolidation. In conclusion, our
                      analysis of the Hevylite Assay in patients with IgG or IgA
                      myeloma from the GMMG-MM5 study did not find evidence to
                      support the general use of HLCr normalization as a response
                      parameter for predicting PFS or OS. However, the
                      differential effects of HLCr normalization depending on the
                      way in which treatment was adapted to response may be of
                      interest for future study designs on response-adapted
                      therapy. Trial Registration: ISRCTN05622749.},
      keywords     = {heavylite assay (Other) / multiple myeloma (Other) /
                      prognostic biomarker (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:41216847},
      doi          = {10.1111/ejh.70061},
      url          = {https://inrepo02.dkfz.de/record/305756},
}