Scientific publications

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

Jul 18, 2024 | Magazine: British Journal of Haematology

Iñaki Ortiz de Landazuri  1 , Aina Oliver-Caldés  1   2 , Marta Español-Rego  1 , Cristina Agulló  3 , María Teresa Contreras  3 , Aintzane Zabaleta  4 , Noemí Puig  3 , Valentín Cabañas  5 , Verónica González-Calle  3 , Inés Zugasti  1 , Susana Inogés  4 , Paula Rodríguez Otero  4 , Beatriz Martin-Antonio  6 , Juan Luis Reguera  7 , Ascensión López-Diaz de Cerio  4 , Juan Ignacio Aróstegui  1 , Mireia Uribe-Herranz  1 , Daniel Benítez-Ribas  1 , Luis Gerardo Rodríguez-Lobato  1 , Europa Azucena González  1 , Natalia Tovar  1 , Paola Charry  1 , Sergio Navarro  1 , Laura Rosiñol  1 , Karen Tréboles  1 , Génesis Mora  1 , Jordi Yagüe  1 , José María Moraleda  5 , Álvaro Urbano-Ispizua  1 , María Victoria Mateos  3 , Mariona Pascal  1 , Bruno Paiva  4 , Manel Juan  1 , Carlos Fernández de Larrea  1


Abstract

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.

CITATION  Br J Haematol. 2024 Jun 18.  doi: 10.1111/bjh.19589