Ibrutinib Use Complicated by Progressive Multifocal Leukoencephalopathy

Abstract

Progressive multifocal leukoencephalopathy (PML) is a fatal demyelinating disease associated with immunocompromised states. We describe a case of PML, which developed after prolonged ibrutinib use and a low burden of chronic lymphocytic leukemia disease. The delay in diagnosis of the patient despite multiple presentations to medical providers across different facilities suggests that there is a lack of awareness of PML as a potential complication of ibrutinib. Treatments with postulated anti-John Cunningham polyomavirus agents and IL-2 were ineffective, likely due to the advanced state of the patient’s disease. Although recent evidence indicates that ibrutinib may enhance cell-mediated immunity, consistent with elevated CD4+ and CD8+ T cells and appropriate T-cell response to mitogens in the patient, ibrutinib-mediated inhibition of the humoral function may contribute to PML pathogenesis. As the duration of ibrutinib use is often indefinite, and the number of indications for ibrutinib continues to grow, recognition and further evaluation of the link between PML and ibrutinib is warranted.

Plasma cell and B cell-targeted treatments for use in advanced multiple sclerosis

“…Some first generation agents have been approved for treating haematological malignancies and graft versus host disease, such as Ibrutinib. This is appears to be a p-glycoprotein substrate, which may limit CNS penetration (van Hoppe et al 2018) and infections following use commonly occur (Tillman et al 2018;Hsiehchen et al 2018). Second generation inhibitors are been developed that have fewer side effects and greater specificity (Wu et al 2016;Pal Singh et al 2018).…”

Progressive Multifocal Leukoencephalopathy in a Patient with Multifocal Neurological Manifestations Caused by Solitary Brainstem Involvement

“…Ibrutinib, a Bruton's tyrosine kinase (BTK) inhibitor, was used in the treatment of various B-cell hematologic malignancies (21). Although several cases of PML after ibrutinib administration have been reported in the past, the further accumulation of knowledge is needed because of the limited number of such reports (22)(23)(24). In the present case, the patient presented with neurological symptoms that first occurred four months after the start of treatment with ibrutinib.…”

Progressive multifocal leukoencephalopathy in the context of newer therapies in hematology and review of new treatment strategies

“…34 Another patient with CLL receiving ibrutinib had her treatment similarly complicated by PML. 35 The most recent case report is that of a patient with mantle cell lymphoma of the conjunctiva, previously treated with rituximab. After 7 years in complete remission, the patient relapsed and was, therefore, treated with ibrutinib.…”

“…A case report of a rituximab pretreated chronic lymphocytic leukemia (CLL) patient who was diagnosed with PML after approximately 1 month of ibrutinib monotherapy has also been reported 34 . Another patient with CLL receiving ibrutinib had her treatment similarly complicated by PML 35 …”