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

Author:

Ortiz de Landazuri Iñaki1ORCID,Oliver‐Caldés Aina12,Español‐Rego Marta1,Agulló Cristina3,Contreras María Teresa3,Zabaleta Aintzane4,Puig Noemí3,Cabañas Valentín5,González‐Calle Verónica3,Zugasti Inés1,Inogés Susana4,Rodríguez Otero Paula4ORCID,Martin‐Antonio Beatriz6,Reguera Juan Luis7,López‐Diaz de Cerio Ascensión4,Aróstegui Juan Ignacio1,Uribe‐Herranz Mireia1,Benítez‐Ribas Daniel1,Rodríguez‐Lobato Luis Gerardo1,González Europa Azucena1,Tovar Natalia1,Charry Paola1,Navarro Sergio1,Rosiñol Laura1ORCID,Tréboles Karen1,Mora Génesis1,Yagüe Jordi1,Moraleda José María5,Urbano‐Ispizua Álvaro1,Mateos María Victoria3ORCID,Pascal Mariona1,Paiva Bruno4,Juan Manel1,Fernández de Larrea Carlos1ORCID

Affiliation:

1. Hospital Clínic de Barcelona Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona Barcelona Spain

2. Hospital Universitari Son Espases Palma de Mallorca Spain

3. Hospital Universitario de Salamanca, Instituto de Investigación Biomédica de Salamanca (IBSAL), Instituto Universitario de Biología Molecular y Celular del Cáncer (USAL‐CSIC), CIBERONC Salamanca Spain

4. Cancer Center Clínica Universidad de Navarra, Centro de Investigación Médica Aplicada (CIMA), IDISNA, CIBERONC Pamplona Spain

5. Hospital Clínico Universitario Virgen de la Arrixaca Instituto Murciano de Investigación Biosanitaria (IMIB‐Pascual Parrilla), Universidad de Murcia Murcia Spain

6. Instituto de Investigación Sanitaria Fundación Jiménez Díaz Madrid Spain

7. Hospital Universitario Virgen del Rocío Instituto de Biomedicina de Sevilla (IBIS/CSIC/CIBERONC), Universidad de Sevilla Sevilla Spain

Abstract

SummaryChimeric 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.

Funder

Instituto de Salud Carlos III

Fundación Científica Asociación Española Contra el Cáncer

Agència de Gestió d'Ajuts Universitaris i de Recerca

Publisher

Wiley

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