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Grant support

This work has been supported in part by grants from the Instituto de Salud Carlos III, Spanish Ministry of Health (FIS PI18/00775, PI19/00669, ICI19/00025 and complementary grant for CONCORD--023), Fondo Europeo de Desarrollo Regional and 2017SGR00792 (AGAUR, Generalitat de Catalunya) and 'La Caixa' Foundation (CP042702). AO--C received funding from the resident grant 'Ajut Clinic--La Pedrera' 2019, granted by Hospital Clinic de Barcelona. As a BITRECS fellow, LGR--L has received funding from the European Union's Horizon 2020 research and innovation program under the Marie Sklodowska--Curie grant agreement ID 754550 and from 'La Caixa' Foundation.

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December 14, 2021
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Article

First report of CART treatment in AL amyloidosis and relapsed/refractory multiple myeloma

Publicated to:Journal For Immunotherapy Of Cancer. 9 (12): e003783- - 2021-12-01 9(12), DOI: 10.1136/jitc-2021-003783

Authors: Oliver-Caldes, Aina; Jimenez, Raquel; Espanol-Rego, Marta; Cibeira, Maria Teresa; Ortiz-Maldonado, Valentin; Quintana, Luis F; Castillo, Paola; Guijarro, Francesca; Tovar, Natalia; Montoro, Mercedes; Benitez-Ribas, Daniel; Bataller, Alex; Gonzalez-Navarro, E Azucena; Lozano, Miquel; Perez-Amill, Lorena; Martin-Antonio, Beatriz; Mena, Mari-Pau; Moreno, David F; Rodriguez-Lobato, Luis Gerardo; Campistol, Josep Maria; Calvo, Gonzalo; Blade, Joan; Rosinol, Laura; Juan, Manel; Pascal, Mariona; Urbano-Ispizua, Alvaro; Fernandez de Larrea, Carlos

Affiliations

Fdn Jimenez Diaz, Inst Invest Sanitaria, Madrid, Spain - Author
Hosp Clin Barcelona, Amyloidosis & Multiple Myeloma Unit, Barcelona, Spain - Author
Hosp Clin Barcelona, Apheresis Unit, Barcelona, Spain - Author
Hosp Clin Barcelona, Clin Trial Unit, Barcelona, Spain - Author
Hosp Clin Barcelona, Dept Clin Pharmacol, Barcelona, Spain - Author
Hosp Clin Barcelona, Dept Immunol, Barcelona, Spain - Author
Hosp Clin Barcelona, Dept Nephrol, Glomerular Dis Unit CSUR, Barcelona, Spain - Author
Hosp Clin Barcelona, Dept Pathol, Barcelona, Spain - Author
Hosp Clin Barcelona, Hematopathol Unit, Barcelona, Spain - Author
Hosp Clin Barcelona, Inst Invest Biomed August Pi Sunyer IDIBAPS, Barcelona, Spain - Author
Hosp Clin Barcelona, Inst Invest Biomed August Pi Sunyer IDIBAPS, Hematol Dept, Barcelona, Spain - Author
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Abstract

Multiple myeloma (MM) remains incurable despite the number of novel therapies that have become available in recent years. Occasionally, a patient with MM will develop an amyloid light-chain (AL) amyloidosis with organ dysfunction. Chimeric antigen receptor T-cell (CART) therapy has become a promising approach in treating hematological malignancies. Our institution has developed a second-generation B-cell maturation antigen (BCMA)-CART which is currently being tested in a clinical trial for relapsed/refractory MM. We present the first reported case, to our knowledge, of a patient with AL amyloidosis and renal involvement in the course of an MM, successfully treated with CART therapy targeting BCMA. The patient received a fractioned dose of 3x10(6)/kg BCMA-CARTs after lymphodepletion. At 3 months from infusion, the patient had already obtained a deep hematological response with negative measurable residual disease by flow cytometry in the bone marrow. After 12 months, the patient remains in hematological stringent complete remission and has achieved an organ renal response with a decrease of 70% of proteinuria. This case suggests that concomitant AL amyloidosis in the setting of MM can benefit from CART therapy, even in patients in which predominant symptoms at the time of treating are caused by AL amyloidosis.

Keywords

chimeric antigenhematological neoplasmsimmunotherapyAdultAl amyloidosisAlbuminuriaArterial embolizationArticleB cell maturation antigenBladder irrigationBone marrowBortezomibBusulfanC reactive proteinCarfilzomibCase reportCell maturationChimeric antigenChimeric antigen receptor t-cell immunotherapyClinical articleClinical outcomeClinical trialCreatinineCyclophosphamideCystoscopyCytokine releaseCytokine release syndromeDaratumumabDexamethasoneDiffusion weighted imagingDrug resistance, neoplasmDrug withdrawalFemaleFerritinFlow cytometryGastrointestinal toxicityHematological neoplasmsHumanHumansImmunoglobulin lambda chainImmunoglobulin light-chain amyloidosisImmunophenotypingImmunotherapyImmunotherapy, adoptiveIntensive care unitIxazomibLenalidomideMelphalanMiddle agedMinimal residual diseaseMultiple cycle treatmentMultiple myelomaNeoplasm recurrence, localNephrotoxicityPhase 3 clinical trialPlatelet countPositron emission tomography-computed tomographyProteinuriaReceptorsVon willebrand factor

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Journal For Immunotherapy Of Cancer due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2021, it was in position 25/245, thus managing to position itself as a Q1 (Primer Cuartil), in the category Oncology. Notably, the journal is positioned above the 90th percentile.

From a relative perspective, and based on the normalized impact indicator calculated from World Citations provided by WoS (ESI, Clarivate), it yields a value for the citation normalization relative to the expected citation rate of: 2.05. This indicates that, compared to works in the same discipline and in the same year of publication, it ranks as a work cited above average. (source consulted: ESI Nov 14, 2024)

This information is reinforced by other indicators of the same type, which, although dynamic over time and dependent on the set of average global citations at the time of their calculation, consistently position the work at some point among the top 50% most cited in its field:

  • Weighted Average of Normalized Impact by the Scopus agency: 1.5 (source consulted: FECYT Feb 2024)
  • Field Citation Ratio (FCR) from Dimensions: 11.7 (source consulted: Dimensions Jul 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-07-06, the following number of citations:

  • WoS: 35
  • Scopus: 28
  • Europe PMC: 9

Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-07-06:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 41.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 41 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 38.2.
  • The number of mentions on the social network X (formerly Twitter): 33 (Altmetric).
  • The number of mentions in news outlets: 1 (Altmetric).

It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

  • The work has been submitted to a journal whose editorial policy allows open Open Access publication.

Leadership analysis of institutional authors

There is a significant leadership presence as some of the institution’s authors appear as the first or last signer, detailed as follows: First Author (Oliver Caldes, Aina) and Last Author (de Larrea, CF).

the author responsible for correspondence tasks has been de Larrea, CF.