{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T19:49:00Z","timestamp":1790970540513,"version":"4.1.0"},"reference-count":25,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T00:00:00Z","timestamp":1762819200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T00:00:00Z","timestamp":1762819200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100006436","name":"Celgene","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006436","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010795","name":"Chugai Pharmaceutical","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010795","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004331","name":"Johnson and Johnson","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004331","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["European J of Haematology"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    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\u2010MM5 trial (EudraCT\u2010No. 2010\u2013019173\u201016) 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\u2010up 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\u2010free survival (PFS; hazard ratio (HR)\u2009=\u20090.75, 95% confidence interval (95% CI)\u2009=\u20090.56\u20131.01,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.06) but not overall survival (OS; HR\u2009=\u20090.94, 95% CI\u2009=\u20090.69\u20131.26,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.66) in multivariable time\u2010dependent 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\u20131.02,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.06). No such effect was observed in study arms in which maintenance was only applied to patients not in CR at the end of consolidation.\n                  <\/jats:p>\n                  <jats:p>In conclusion, our analysis of the Hevylite Assay in patients with IgG or IgA myeloma from the GMMG\u2010MM5 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\u2010adapted therapy.<\/jats:p>\n                  <jats:p>\n                    <jats:bold>Trial Registration:<\/jats:bold>\n                    ISRCTN05622749.\n                  <\/jats:p>","DOI":"10.1111\/ejh.70061","type":"journal-article","created":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T11:05:46Z","timestamp":1762859146000},"page":"226-234","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Prognostic Impact of the Hevylite Assay in Patients With\n                    <scp>IgG<\/scp>\n                    or\n                    <scp>IgA<\/scp>\n                    Multiple Myeloma Treated Within the\n                    <scp>GMMG<\/scp>\n                    \u2010\n                    <scp>MM5<\/scp>\n                    Trial"],"prefix":"10.1111","volume":"116","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-3588-6376","authenticated-orcid":false,"given":"Tim","family":"Richardson","sequence":"first","affiliation":[{"name":"Department of Internal Medicine I University Hospital Cologne  Cologne 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":"Heidelberg Myeloma Center, Internal Medicine V, Hematology, Oncology and Rheumatology Heidelberg University Hospital  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5539-580X","authenticated-orcid":false,"given":"Ekaterina","family":"Menis","sequence":"additional","affiliation":[{"name":"Heidelberg Myeloma Center, Internal Medicine V, Hematology, Oncology and Rheumatology Heidelberg University Hospital  Heidelberg 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Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4767-3275","authenticated-orcid":false,"given":"Mathias","family":"H\u00e4nel","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine III  Chemnitz Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Britta","family":"Besemer","sequence":"additional","affiliation":[{"name":"Department of Hematology, Oncology and Immunology University Hospital T\u00fcbingen  T\u00fcbingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amelie","family":"Boquoi","sequence":"additional","affiliation":[{"name":"Department of Hematology University Clinic Essen  Essen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Igor Wolfgang","family":"Blau","sequence":"additional","affiliation":[{"name":"Medical Clinic Charit\u00e9 University Medicine Berlin  Berlin 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