DESCARTES-08 + fludarabine + cyclophosphamide

DESCARTES-08 + fludarabine + cyclophosphamide describes a combination therapy involving DESCARTES-08, an autologous mRNA CAR-T cell therapy targeting B-cell maturation antigen (BCMA), with fludarabine and cyclophosphamide, two cytotoxic chemotherapy agents commonly used as lymphodepleting preconditioning regimens in CAR-T protocols. DESCARTES-08 consists of patient-derived CD8+ T cells engineered with mRNA to express an anti-BCMA CAR for a controlled, transient duration (typically about one week), thereby enabling targeted depletion of BCMA-expressing cells (such as malignant plasma cells in multiple myeloma or autoreactive B cells in autoimmune disease) while mitigating risks associated with long-term CAR expression. Fludarabine and cyclophosphamide are administered intravenously and synergistically induce lymphodepletion, improving CAR-T engraftment and efficacy; both are DNA-damaging cytotoxic agents—fludarabine is a purine analog and cyclophosphamide is an alkylating agent[1][3][4][6]. This combination is under investigation in clinical trial settings for relapsed/refractory multiple myeloma, generalized myasthenia gravis, and other autoimmune diseases[1][3][5][7].