Universität zu Köln

Richardson, Tim ORCID: 0009-0006-3588-6376, Holtick, Udo ORCID: 0000-0002-5543-0257, Frenking, Jan-Hendrik ORCID: 0009-0001-9682-2601, Tharmaseelan, Hishan ORCID: 0009-0002-5680-8714, Balke-Want, Hyatt ORCID: 0000-0002-5963-7626, Flümann, Ruth ORCID: 0000-0002-7147-7557, Mai, Elias Karl ORCID: 0000-0002-6226-1252, Sauer, Sandra, Teipel, Raphael ORCID: 0000-0002-9985-6583, von Bonin, Malte ORCID: 0000-0002-2995-3230, Hallek, Michael ORCID: 0000-0002-7425-4455, Scheid, Christof ORCID: 0009-0007-6539-226X and Gödel, Philipp ORCID: 0000-0001-7887-8313 (2025). Sequential BCMA CAR T-cell therapy in refractory multiple myeloma. Blood Advances, 9 (18). pp. 4624-4630. Elsevier. ISSN 2473-9529

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Abstract

Multiple myeloma (MM) relapsing after B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T-cell treatment remains a therapeutic challenge. Data on re-exposure to CAR T-cell therapy targeting the same antigen are scarce. We analyzed 10 heavily pretreated patients with RRMM at 3 medical centers treated with the commercially approved CAR T-cell therapy product idecabtagene vicleucel in a real-world setting. Upon relapse, all patients received ciltacabtagene autoleucel as a second CAR T-cell therapy infusion, with bridging treatments permitted between both therapies. Sequential therapy with BCMA-directed CAR T-cell therapy was safe, with no higher-grade immune-cell–associated side effects or new safety signals. We found robust CAR T-cell therapy expansion and high response rates (100% with at least very good partial response, with 60% achieving minimal residual disease negativity), with an estimated progression-free survival of 64.8% (95% confidence interval, 39%-100%) at 6 months after the second CAR T-cell treatment. Duration of response to first CAR T-cell therapy was predictive for durable responses to the second CAR T-cell therapy product. Loss of BCMA antigen occurred in only 1 of 3 patients relapsing after ciltacabtagene autoleucel. Two of three relapsing patients died within a year, and showed no further response to bispecific antibody treatment. To our knowledge, this study provides the first real-world evidence that sequential treatment with 2 different commercially approved BCMA CAR T-cell therapy products is both feasible and effective, particularly in patients with prolonged responses to initial BCMA CAR T-cell therapy.

Item Type:	Article
Creators:	Creators Email ORCID ORCID Put Code Richardson, Tim UNSPECIFIED https://orcid.org/0009-0006-3588-6376 UNSPECIFIED Holtick, Udo UNSPECIFIED https://orcid.org/0000-0002-5543-0257 UNSPECIFIED Frenking, Jan-Hendrik UNSPECIFIED https://orcid.org/0009-0001-9682-2601 UNSPECIFIED Tharmaseelan, Hishan UNSPECIFIED https://orcid.org/0009-0002-5680-8714 UNSPECIFIED Balke-Want, Hyatt UNSPECIFIED https://orcid.org/0000-0002-5963-7626 UNSPECIFIED Flümann, Ruth UNSPECIFIED https://orcid.org/0000-0002-7147-7557 UNSPECIFIED Mai, Elias Karl UNSPECIFIED https://orcid.org/0000-0002-6226-1252 UNSPECIFIED Sauer, Sandra UNSPECIFIED UNSPECIFIED UNSPECIFIED Teipel, Raphael UNSPECIFIED https://orcid.org/0000-0002-9985-6583 UNSPECIFIED von Bonin, Malte UNSPECIFIED https://orcid.org/0000-0002-2995-3230 UNSPECIFIED Hallek, Michael UNSPECIFIED https://orcid.org/0000-0002-7425-4455 UNSPECIFIED Scheid, Christof UNSPECIFIED https://orcid.org/0009-0007-6539-226X UNSPECIFIED Gödel, Philipp UNSPECIFIED https://orcid.org/0000-0001-7887-8313 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-798597
Identification Number:	10.1182/bloodadvances.2025016712
Journal or Publication Title:	Blood Advances
Volume:	9
Number:	18
Page Range:	pp. 4624-4630
Number of Pages:	7
Date:	23 September 2025
Publisher:	Elsevier
ISSN:	2473-9529
Language:	English
Faculty:	Central Institutions / Interdisciplinary Research Centers 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
['eprint_fieldname_oa_funders' not defined]:	Publikationsfonds UzK
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/79859