A report of progressive multifocal leukoencephalopathy during adjuvant abemaciclib for breast cancer.

Drugs inhibiting the cyclin-dependent kinases (CDK) 4 and 6 are widely used for the treatment of luminal breast cancer, in the adjuvant and in the metastatic setting, and adverse events are well-known. Progressive multifocal leukoencephalopathy (PML) is classically linked to immunosuppression. We present a case of progressive multifocal leukoencephalopathy that developed during adjuvant abemaciclib therapy in a seventy-year-old woman diagnosed with locally advanced ductal carcinoma of the breast. Neurological impairment developed after 18 months of initiating abemaciclib and in imaging tests a left frontal brain lesion appeared. Metastasis was excluded and the evidence of the John Cunningham polyomavirus (JCPyV) genome, both in the blood and in the cerebrospinal fluid, supported the diagnosis of PML. We did not identify significant immune blood cell counts alterations, nor other causes of immunosuppression; the patient was not treated with other immunosuppressive drugs. We speculate that different immune mechanism alterations related to abemaciclib, which has a high penetration rate in the brain, may be involved in an increased risk of JCPyV reactivation and consequently PML development.