Corticosteroids ameliorate CAR T-cell-induced cytokine-release syndrome without inhibiting multiple myeloma treatment - PubMed
4 days ago
- #CAR T-cell therapy
- #cytokine-release syndrome
- #multiple myeloma
- Corticosteroids like dexamethasone can alleviate cytokine-release syndrome (CRS) caused by CAR T-cell therapy without compromising its effectiveness in treating multiple myeloma (MM).
- A co-culture model involving THP-1 monocytic cells, anti-BCMA CAR T cells, and BCMA+ target cells demonstrated increased IL-6 and MCP-1 levels, mimicking CRS conditions.
- A murine CRS model was developed, incorporating THP-1 cells, MM.1S-veff-Luc myeloma cells, and CAR-BCMA T cells, showing dexamethasone effectively reduced CRS symptoms.
- Dexamethasone treatment led to faster elimination of myeloma cells and higher levels of CAR T cells in the spleen, even with dexamethasone-resistant cell lines.
- Clinical trial data (NCT03602612) showed CAR T-cell levels continued to rise in patients receiving corticosteroids, supporting their use in managing CRS without hindering therapy.
- The findings advocate for further research into corticosteroid regimens that optimize CRS management while preserving CAR T-cell anti-tumor activity.