Serum mass spectrometry for treatment monitoring in patients with multiple myeloma receiving ARI0002h CAR T-cells.
Iñaki Ortiz de LandazuriAina Oliver-CaldésMarta Español-RegoCristina AgullóMaría Teresa ContrerasAintzane ZabaletaNoemí PuigValentín CabañasVerónica González-CalleInés ZugastiSusana InogésPaula Rodriguez OteroBeatriz Martin-AntonioJuan Luis RegueraAscensión López-Diaz de CerioJuan Ignacio ArósteguiMireia Uribe-HerranzDaniel Benítez-RibasLuis Gerardo Rodríguez-LobatoEuropa Azucena GonzálezNatalia TovarPaola CharrySergio NavarroLaura RosinolKaren TrébolesGénesis MoraJordi YagüeJosé María MoraledaÁlvaro Urbano-IspizuaMaria-Victoria Mateos-MantecaMariona PascalBruno PaivaManel JuanCarlos Fernández de LarreaPublished in: British journal of haematology (2024)
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.
Keyphrases
- mass spectrometry
- multiple myeloma
- multiple sclerosis
- ms ms
- liquid chromatography
- high resolution
- capillary electrophoresis
- gas chromatography
- bone marrow
- high performance liquid chromatography
- growth factor
- flow cytometry
- acute myeloid leukemia
- rheumatoid arthritis
- mesenchymal stem cells
- tandem mass spectrometry
- acute lymphoblastic leukemia
- diffuse large b cell lymphoma
- binding protein
- systemic lupus erythematosus
- climate change
- hodgkin lymphoma
- combination therapy
- simultaneous determination
- medical students