{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T21:03:06Z","timestamp":1769115786060,"version":"3.49.0"},"reference-count":13,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,8,30]],"date-time":"2025-08-30T00:00:00Z","timestamp":1756512000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["eJHaem"],"published-print":{"date-parts":[[2025,10]]},"abstract":"ABSTRACT<\/jats:title>\n \n Background<\/jats:title>\n Relapsed\/refractory multiple myeloma (RRMM) remains difficult to treat despite advances in therapy. B\u2010cell maturation antigen (BCMA)\u2010directed chimeric antigen receptor T\u2010cell (CAR\u2010T) therapies, such as idecabtagene vicleucel (ide\u2010cel) and ciltacabtagene autoleucel (cilta\u2010cel), have improved outcomes, yet many patients relapse within a year. Current International Myeloma Working Group (IMWG) criteria for deep response require prolonged observation. Early, practical biomarkers could enable timelier risk stratification and intervention.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To evaluate whether serum free light\u2010chain (FLC) suppression at Day +28 after BCMA\u2010directed CAR\u2010T infusion predicts progression\u2010free survival (PFS) and overall survival (OS) in RRMM.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n We conducted a retrospective multicenter analysis of 80 consecutive RRMM patients treated with in\u2010label ide\u2010cel or cilta\u2010cel between January 2022 and July 2024 at four tertiary centers. Patients with oligo\u2010\/non\u2010secretory myeloma were excluded. FLC suppression\u2014defined as undetectable\n \u03ba<\/jats:italic>\n or\n \u03bb<\/jats:italic>\n light chains using the Freelite assay\u2014was assessed at Day +28 (window: Days 27\u201331) and at 3 months post\u2010infusion. Survival analyses used a landmark approach from Day +28. Multivariate Cox regression adjusted for prior BCMA\/T\u2010cell\u2010directed therapy, high\u2010risk cytogenetics (HRC), extramedullary disease (EMD), and pre\u2010CAR\u2010T response status.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n At Day +28, 51 patients (63.8%) achieved FLC suppression. Median follow\u2010up was 11.8 months. FLC suppression correlated with markedly longer median PFS (23.4\u00a0vs. 4.1 months,\n p<\/jats:italic>\n < 0.001) and improved OS (12\u2010month OS: 88.0%\u00a0vs. 18.1%,\n p<\/jats:italic>\n = 0.013). Benefits were observed across CAR\u2010T products, but suppression rates were higher with cilta\u2010cel (81.6%) than ide\u2010cel (45.2%). HRC remained an adverse factor even in suppressed patients, while EMD showed a less consistent effect. In multivariate analysis, absence of FLC suppression independently predicted inferior PFS.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n FLC suppression at Day +28 post\u2010CAR\u2010T is an early, inexpensive biomarker associated with superior PFS and OS in RRMM. It often precedes IMWG\u2010defined complete response and could support risk\u2010adapted post\u2010CAR\u2010T management. Prospective validation is warranted to integrate FLC suppression into early response assessment strategies.<\/jats:p>\n <\/jats:sec>\n \n Trial Registration<\/jats:title>\n The authors have confirmed clinical trial registration is not needed for this submission<\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/jha2.70139","type":"journal-article","created":{"date-parts":[[2025,8,30]],"date-time":"2025-08-30T10:28:36Z","timestamp":1756549716000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Early Free Light\u2010Chain Suppression as a Prognostic Marker in Relapsed and Refractory Myeloma Patients Treated With BCMA\u2010Directed CAR\u2010T Cells"],"prefix":"10.1002","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-3588-6376","authenticated-orcid":false,"given":"Tim","family":"Richardson","sequence":"first","affiliation":[{"name":"Department I of Internal Medicine, Medical Faculty and University Hospital of Cologne University of Cologne Cologne Germany"},{"name":"Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf (CIO ABCD) Aachen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hishan","family":"Tharmaseelan","sequence":"additional","affiliation":[{"name":"Department I of Internal Medicine, Medical Faculty and University Hospital of Cologne University of Cologne Cologne Germany"},{"name":"Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf (CIO ABCD) Aachen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guido","family":"Kobbe","sequence":"additional","affiliation":[{"name":"Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf (CIO ABCD) Aachen Germany"},{"name":"Department of Hematology, Oncology, and Clinical Immunology Heinrich Heine University D\u00fcsseldorf D\u00fcsseldorf Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-1699-9478","authenticated-orcid":false,"given":"Ben\u2010Niklas","family":"Baermann","sequence":"additional","affiliation":[{"name":"Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf (CIO ABCD) Aachen Germany"},{"name":"Department of Hematology, Oncology, and Clinical Immunology Heinrich Heine University D\u00fcsseldorf D\u00fcsseldorf Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tobias A. W.","family":"Holderried","sequence":"additional","affiliation":[{"name":"Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf (CIO ABCD) Aachen Germany"},{"name":"Department of Hematology, Oncology, Stem Cell Transplantation, Immune and Cell Therapy, Clinical Immunology and Rheumatology University Hospital Bonn Bonn Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Friederike","family":"Schmitz","sequence":"additional","affiliation":[{"name":"Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf (CIO ABCD) Aachen Germany"},{"name":"Department of Hematology, Oncology, Stem Cell Transplantation, Immune and Cell Therapy, Clinical Immunology and Rheumatology University Hospital Bonn Bonn Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martina","family":"Crysandt","sequence":"additional","affiliation":[{"name":"Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf (CIO ABCD) Aachen Germany"},{"name":"Department of Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, Medical Faculty University Hospital Aachen Aachen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philipp","family":"G\u00f6del","sequence":"additional","affiliation":[{"name":"Department I of Internal Medicine, Medical Faculty and University Hospital of Cologne University of Cologne Cologne Germany"},{"name":"Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf (CIO ABCD) Aachen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nathan","family":"Wolfensberger","sequence":"additional","affiliation":[{"name":"Department I of Internal Medicine, Medical Faculty and University Hospital of Cologne University of Cologne Cologne Germany"},{"name":"Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf (CIO ABCD) Aachen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Sch\u00fctte","sequence":"additional","affiliation":[{"name":"Department I of Internal Medicine, Medical Faculty and University Hospital of Cologne University of Cologne Cologne Germany"},{"name":"Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf (CIO ABCD) Aachen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7425-4455","authenticated-orcid":false,"given":"Michael","family":"Hallek","sequence":"additional","affiliation":[{"name":"Department I of Internal Medicine, Medical Faculty and University Hospital of Cologne University of Cologne Cologne Germany"},{"name":"Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf (CIO ABCD) Aachen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christof","family":"Scheid","sequence":"additional","affiliation":[{"name":"Department I of Internal Medicine, Medical Faculty and University Hospital of Cologne University of Cologne Cologne Germany"},{"name":"Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf (CIO ABCD) Aachen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Udo","family":"Holtick","sequence":"additional","affiliation":[{"name":"Department I of Internal Medicine, Medical Faculty and University Hospital of Cologne University of Cologne Cologne Germany"},{"name":"Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf (CIO ABCD) Aachen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,8,30]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2213614"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2303379"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2022017848"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102023\u2010178933"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1158\/2643\u20103230.BCD\u201023\u20100134"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3026(21)00057-0"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41375\u2010023\u201002129\u2010y"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2024024965"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2024850"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41408\u2010024\u201001191\u20108"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102023\u2010177749"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2022.282510"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/hem3.70070"}],"container-title":["eJHaem"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jha2.70139","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,25]],"date-time":"2025-10-25T10:53:19Z","timestamp":1761389599000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jha2.70139"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,30]]},"references-count":13,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2025,10]]}},"alternative-id":["10.1002\/jha2.70139"],"URL":"https:\/\/doi.org\/10.1002\/jha2.70139","archive":["Portico"],"relation":{},"ISSN":["2688-6146","2688-6146"],"issn-type":[{"value":"2688-6146","type":"print"},{"value":"2688-6146","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,30]]},"assertion":[{"value":"2025-07-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication 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