Serum mass spectrometry for treatment monitoring in patients with multiple myeloma receiving ARI0002h CAR T-cells

Chimeric antigen receptor (CAR) T-cell therapies have increased the patients with relapsed/refractory multiple myeloma (RRMM) in whom standard electrophoretic techniques fail to detect the M-protein. Quantitative immunoprecipitation mass spectrometry (QIP-MS) can accurately measure serum M-protein w...

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Bibliographic Details
Published in:	British journal of haematology Vol. 205; no. 4; pp. 1346 - 1355
Main Authors:	Ortiz de Landazuri, Iñaki, Oliver-Caldés, Aina, Español-Rego, Marta, Agulló, Cristina, Contreras, María Teresa, Zabaleta, Aintzane, Puig, Noemí, Cabañas, Valentín, González-Calle, Verónica, Zugasti, Inés, Inogés, Susana, Rodríguez Otero, Paula, Martin-Antonio, Beatriz, Reguera, Juan Luis, López-Diaz de Cerio, Ascensión, Aróstegui, Juan Ignacio, Uribe-Herranz, Mireia, Benítez-Ribas, Daniel, Rodríguez-Lobato, Luis Gerardo, González, Europa Azucena, Tovar, Natalia, Charry, Paola, Navarro, Sergio, Rosiñol, Laura, Tréboles, Karen, Mora, Génesis, Yagüe, Jordi, Moraleda, José María, Urbano-Ispizua, Álvaro, Mateos, María Victoria, Pascal, Mariona, Paiva, Bruno, Juan, Manel, Fernández de Larrea, Carlos
Format:	Journal Article
Language:	English
Published:	England Blackwell Publishing Ltd 01-10-2024
Subjects:	Adult Aged Antibodies, Monoclonal, Humanized - therapeutic use B-Cell Maturation Antigen Cell therapy Chimeric antigen receptors Female Flow cytometry Humans Immunoprecipitation Immunotherapy, Adoptive - methods Male Mass spectrometry Mass Spectrometry - methods Mass spectroscopy Middle Aged Monoclonal antibodies Multiple myeloma Multiple Myeloma - blood Multiple Myeloma - therapy Myeloma Proteins - analysis Nerve growth factor Receptors, Chimeric Antigen Scientific imaging mass spectrometry multiple myeloma CAR T‐cell therapy
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Summary:	Chimeric antigen receptor (CAR) T-cell therapies have increased the patients with relapsed/refractory multiple myeloma (RRMM) in whom standard electrophoretic techniques fail to detect the M-protein. Quantitative immunoprecipitation mass spectrometry (QIP-MS) can accurately measure serum M-protein with high sensitivity, and identify interferences caused by therapeutic monoclonal antibodies. Here, we investigate the outcome of QIP-MS in 33 patients treated with the academic BCMA-directed CAR T-cell ARI0002h (Cesnicabtagene Autoleucel). QIP-MS offered more detailed insights than serum immunofixation (sIFE), identifying glycosylated M-proteins and minor additional peaks. Moreover, the potential interferences owing to daratumumab or tocilizumab treatments were successfully detected. When analysing different assay platforms during patient's monitoring after ARI0002h administration, we observed that QIP-MS showed a high global concordance (78.8%) with sIFE, whereas it was only moderate (55.6%) with bone marrow (BM)-based next-generation flow cytometry (NGF). Furthermore, QIP-MS consistently demonstrated the lowest negativity rate across the different timepoints (27.3% vs. 60.0% in months 1 and 12, respectively). Patients with QIP-MS(+)/BM-based NGF(-) showed a non-significant shorter median progression free survival than those with QIP-MS(-)/BM-based NGF(-). In summary, we show the first experience to our knowledge demonstrating that QIP-MS could be particularly useful as a non-invasive technique when evaluating response after CAR T-cell treatment in MM.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0007-1048 1365-2141 1365-2141
DOI:	10.1111/bjh.19589