Disease-related baseline cerebrospinal fluid proteomic variation refines biomarker interpretation before CAR-T therapy
Nomiyama, T.; Setoyama, D.; Yamanaka, I.; Shimo, M.; Miyawaki, K.; Yamauchi, T.; Jinnouchi, F.; Sakoda, T.; Sasaki, K.; Nakagaki, H.; Takigawa, K.; Taniguchi, S.; Shima, T.; Mori, Y.; Kanaji, S.; Kato, T. A.; Kikushige, Y.; Akashi, K.; Kunisaki, Y.; Kato, K.
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Pre-infusion cerebrospinal fluid (CSF) proteomics may enable risk stratification for immune effector cell-associated neurotoxicity syndrome (ICANS) after chimeric antigen receptor T-cell therapy, but disease-specific baseline variation may influence biomarker interpretation. We compared pre-infusion CSF proteomic profiles from 28 patients with diffuse large B-cell lymphoma (DLBCL) and 9 with multiple myeloma (MM). Although principal component analysis showed substantial overlap, orthoPLS-DA identified significant disease-associated discrimination supported by permutation testing. Proteins contributing to this separation were enriched for plasma cell-related, extracellular, and metabolic signatures. ICANS occurred in 7 of 28 DLBCL patients but in none of the 9 MM patients. MM cases aligned with the ICANS-negative group in binary analysis while remaining distinct from both DLBCL subgroups in three-group analysis. These findings indicate that pre-infusion CSF proteomics captures disease-specific molecular structure that should be considered when developing and interpreting biomarkers of CAR-T-associated neurotoxicity.
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