Universität zu Köln

Richardson, Tim ORCID: 0009-0006-3588-6376, Tharmaseelan, Hishan ORCID: 0009-0002-5680-8714, Kobbe, Guido ORCID: 0000-0002-9745-8813, Baermann, Ben‐Niklas ORCID: 0009-0000-1699-9478, Holderried, Tobias A. W. ORCID: 0000-0002-2474-523X, Schmitz, Friederike ORCID: 0000-0002-5271-1088, Crysandt, Martina ORCID: 0000-0002-7450-3394, Gödel, Philipp ORCID: 0000-0001-7887-8313, Wolfensberger, Nathan, Schütte, Daniel, Hallek, Michael ORCID: 0000-0002-7425-4455, Scheid, Christof ORCID: 0009-0007-6539-226X and Holtick, Udo ORCID: 0000-0002-5543-0257 (2025). Early Free Light‐Chain Suppression as a Prognostic Marker in Relapsed and Refractory Myeloma Patients Treated With BCMA‐Directed CAR‐T Cells. eJHaem, 6 (5). pp. 1-5. Wiley. ISSN 2688-6146

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Abstract

[Artikel-Nr.: 6:e70139] Background: Relapsed/refractory multiple myeloma (RRMM) remains difficult to treat despite advances in therapy. B‐cell maturation antigen (BCMA)‐directed chimeric antigen receptor T‐cell (CAR‐T) therapies, such as idecabtagene vicleucel (ide‐cel) and ciltacabtagene autoleucel (cilta‐cel), 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. Objective: To evaluate whether serum free light‐chain (FLC) suppression at Day +28 after BCMA‐directed CAR‐T infusion predicts progression‐free survival (PFS) and overall survival (OS) in RRMM. Methods: We conducted a retrospective multicenter analysis of 80 consecutive RRMM patients treated with in‐label ide‐cel or cilta‐cel between January 2022 and July 2024 at four tertiary centers. Patients with oligo‐/non‐secretory myeloma were excluded. FLC suppression—defined as undetectable κ or λ light chains using the Freelite assay—was assessed at Day +28 (window: Days 27–31) and at 3 months post‐infusion. Survival analyses used a landmark approach from Day +28. Multivariate Cox regression adjusted for prior BCMA/T‐cell‐directed therapy, high‐risk cytogenetics (HRC), extramedullary disease (EMD), and pre‐CAR‐T response status. Results: At Day +28, 51 patients (63.8%) achieved FLC suppression. Median follow‐up was 11.8 months. FLC suppression correlated with markedly longer median PFS (23.4 vs. 4.1 months, p < 0.001) and improved OS (12‐month OS: 88.0% vs. 18.1%, p = 0.013). Benefits were observed across CAR‐T products, but suppression rates were higher with cilta‐cel (81.6%) than ide‐cel (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. Conclusions: FLC suppression at Day +28 post‐CAR‐T is an early, inexpensive biomarker associated with superior PFS and OS in RRMM. It often precedes IMWG‐defined complete response and could support risk‐adapted post‐CAR‐T management. Prospective validation is warranted to integrate FLC suppression into early response assessment strategies. Trial Registration: The authors have confirmed clinical trial registration is not needed for this submission.

Item Type:	Article
Creators:	Creators Email ORCID ORCID Put Code Richardson, Tim UNSPECIFIED https://orcid.org/0009-0006-3588-6376 UNSPECIFIED Tharmaseelan, Hishan UNSPECIFIED https://orcid.org/0009-0002-5680-8714 UNSPECIFIED Kobbe, Guido UNSPECIFIED https://orcid.org/0000-0002-9745-8813 UNSPECIFIED Baermann, Ben‐Niklas UNSPECIFIED https://orcid.org/0009-0000-1699-9478 UNSPECIFIED Holderried, Tobias A. W. UNSPECIFIED https://orcid.org/0000-0002-2474-523X UNSPECIFIED Schmitz, Friederike UNSPECIFIED https://orcid.org/0000-0002-5271-1088 UNSPECIFIED Crysandt, Martina UNSPECIFIED https://orcid.org/0000-0002-7450-3394 UNSPECIFIED Gödel, Philipp UNSPECIFIED https://orcid.org/0000-0001-7887-8313 UNSPECIFIED Wolfensberger, Nathan UNSPECIFIED UNSPECIFIED UNSPECIFIED Schütte, Daniel UNSPECIFIED UNSPECIFIED UNSPECIFIED Hallek, Michael UNSPECIFIED https://orcid.org/0000-0002-7425-4455 UNSPECIFIED Scheid, Christof UNSPECIFIED https://orcid.org/0009-0007-6539-226X UNSPECIFIED Holtick, Udo UNSPECIFIED https://orcid.org/0000-0002-5543-0257 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-802334
Identification Number:	10.1002/jha2.70139
Journal or Publication Title:	eJHaem
Volume:	6
Number:	5
Page Range:	pp. 1-5
Number of Pages:	5
Date:	30 October 2025
Publisher:	Wiley
ISSN:	2688-6146
Language:	English
Faculty:	Faculty of Medicine
Divisions:	Faculty of Medicine > Innere Medizin > Klinik I für Innere Medizin - Hämatologie und Onkologie Faculty of Medicine > Weitere > Centrum für integrierte Onkologie (CIO)
Subjects:	Medical sciences Medicine
Uncontrolled Keywords:	Keywords Language biomarker ; CAR-T cells ; multiple myeloma ; response assessment English
['eprint_fieldname_oa_funders' not defined]:	Publikationsfonds UzK
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/80233