To review the literature of progressive multifocal leukoencephalopathy (PML) caused by multiple myeloma and to present a case of PML in a patient with relapsed multiple myeloma on pomalidomide therapy.

PML is a rare often fatal demyelinating disease of the central nervous system caused by reactivation of the Polyomavirus JC. While originally described in HIV/AIDS prior to the advent of highly active antiretroviral therapy, PML is now seen more commonly in individuals who are iatrogenically immunocompromised, such as organ transplant recipients and patients with autoimmune disease requiring immunomodulatory therapy. PML has also been observed in hematologic malignancies, namely lymphoma, chronic lymphocytic leukemia, and acute leukemia.  PML in the setting of multiple myeloma is less common.

A 67-year-old woman with a history of relapsed, refractory IgA lambda multiple myeloma treated with pomalidomide and dexamethasone presented with two weeks of right-hand clumsiness, word finding difficulties, dysphagia, and balance complaints. MRI brain imaging demonstrated bilateral scattered confluent cerebral hemispheric white matter disease and a negative serum and CSF work up. Symptoms and imaging progressed despite discontinuing chemotherapy. A diagnosis of PML was confirmed with repeat CSF demonstrating JC virus DNA by PCR.

A literature review was performed for PML and multiple myeloma using PUBMED and EMBASE.

A literature review identified 17 cases of PML in patients with a diagnosis of multiple myeloma. PML has been reported with a variety of treatments for multiple myeloma, including melphalan, cyclophosphamide, thalidomide, lenalidomide, pomalidomide, Bortezomib/dexamethasone, Ixazomib/dexamethasone, vincristine/doxorubicin, and autologous stem cell transplant. No cases of PML in multiple myeloma were identified with the monoclonal antibody treatments anti-SLAMF7 and anti-CD38.

PML has been observed in hematologic malignancy but is rarely seen in multiple myeloma. The development of PML has been associated with most of the common treatments for multiple myeloma except for the new novel monoclonal antibody therapies.