NCMP-22. FLUDARABINE NEUROTOXICITY IN PATIENTS UNDERGOING CAR T-CELL THERAPY - A REPORT OF 2 CASES

Fludarabine is a purine analog used in the treatment of chronic lymphocytic leukemia (CLL) and as part of immunosuppressive/lymphodepleting regimens in allogeneic stem cell transplant and chimeric antigen receptor (CAR) T-cell therapy. It induces cellular cytotoxicity through multiple mechanisms, ultimately leading to the inhibition of DNA synthesis. Although myelosuppression is the primary dose-limiting side effect of fludarabine, there have been reported cases of delayed-onset neurological symptoms, such as progressive visual impairments, dementia, ataxia, hemiparesis, quadriparesis, and blindness. These symptoms have been observed in patients receiving fludarabine alone or as part of preconditioning treatments for CAR T-cell therapy. The neurological abnormalities are characterized by leukoencephalopathies and can manifest as posterior reversible encephalopathy (PRES), acute toxic leukoencephalopathy (ATL), or other leukoencephalopathy (OLE). We present two cases of patients who underwent fludarabine conditioning before CAR T-cell therapy, exhibiting late-onset and progressive changes in vision and encephalopathy. These symptoms differ in timing and pattern from the neurotoxicities commonly associated with CAR T-cell therapy. Nonetheless, given the overlapping neurological toxicities seen with both CAR-T cell therapy and fludarabine, it is important to consider implementing thorough screening measures to modify preconditioning fludarabine dose intensity, particularly for patients with advanced disease, renal insufficiency, or other risk factors to limit fludarabine-associated adverse effects.