The central nervous system (CNS) is rarely involved in
plasma cell neoplasms (
PCN), especially in patients with advanced disease, harboring poor prognostic
chromosomal abnormalities. The prognosis after development of CNS is poor, with a median survival of 2-6 months. Here, we present a 56-year-old woman with isolated CNS relapse of
plasma cell leukemia who was admitted to our hospital with
back pain, thigh
pain, and
dysuria. Morphological examination of the cerebrospinal fluid (CSF) confirmed the presence of relapsed
plasma cell leukemia, whereas active myeloma lesions were not detectable outside the CNS. Her symptoms did not improve with high doses of
methotrexate or intrathecal
chemotherapy. However, one cycle of combination
therapy with
lenalidomide and
dexamethasone led to the improvement in clinical symptoms, with complete response seen in the CSF morphology. After 13 cycles, she developed a hematological relapse but maintained complete response in the CSF. The efficacy of
lenalidomide in CSF
PCN was sporadically reported, and the CNS penetrance of
lenalidomide was demonstrated in animal models; however, its efficacy in CNS
PCN has not been established. The current case supports the efficacy of combination
therapy with
lenalidomide as a new therapeutic strategy for CNS
PCN.