Cytokine release syndrome (CRS) is a limiting factor for the application of chimera antigen receptor (CAR) T-cell therapy. Plasma biomarkers may help enhance CAR-T therapy for multiple myeloma (MM), according to a letter to the editor published in the Journal of Hematology & Oncology.
CAR T-cell therapy is a promising new treatment for relapsed or refractory MM (RRMM). However, CAR-T therapy has been found to alter platelet-activating factor (PAF) synthesis in these patients. Targeting PAF remodeling may improve the effectiveness of CAR-T therapy in patients with RRMM.
The authors analyzed profile changes of metabolites and lipids in plasma from 17 patients with RRMM who previously received CAR-T therapy.
The authors separated patients into a cytokine release syndrome (CRS) group and a comparative efficacy group. Glycerophosphocholine (GPC) is a PAF-like molecule. At day 30, patients with CRS had a decreased plasma level of GPC compared with patients without CRS. This suggests that CRS is associated with the activation of GPC oxidative phosphorylation and the intensification of PAF synthesis.
Lysophosphatidylcholines (lysoPCs), which were catalyzed by lysoPC acyltransferase (LPCAT) were also elevated, and served as a “distinct metabolic signature” of patients with RRMM. The authors suggested that LPCAT1 may be a potential target for CAR-T therapy, as it may act as an oncogene in MM.
“Collectively, targeting PAF remodeling may be a promising strategy to enhance MM CAR-T therapy,” the authors concluded.
Ke M, Kang L, Wang L, et al. CAR-T therapy alters synthesis of platelet-activating factor in multiple myeloma patients. J Hematol Oncol. 2021;14(1):90. doi:10.1186/s13045-021-01101-6