Treating Progressive Multifocal Leukoencephalopathy (Pml) with Pembrolizumab: A Single Institution Experience

ABSTRACT

BACKGROUND: PML is a rapidly progressive demyelinating disease, occurring in immunocompromised patients due to the opportunistic JC virus. The highest mortality rates are seen among patients with cancer treated with immunosuppressive therapy and for whom immune reconstitution is not possible. In 2019, the National Institutes of Health reported clinical benefit in patients with PML treated with pembrolizumab. We report our institutional experience with pembrolizumab for three patients with PML after exposure to rituximab and other chemotherapy. CASE PRESENTATION The first patient was a 75-year-old woman with a history of psoriatic arthritis and bullous pemphigoid treated with rituximab. Eight months after rituximab exposure she presented with right hemiparesis and word-finding difficulty. PML was diagnosed based on positive JC virus DNA in cerebrospinal fluid by PCR. She received two doses of pembrolizumab with improvement in her neurological symptoms. Shortly after her second dose she contracted COVID-19 and died at her nursing home. The second patient was a 47-year-old man with a history of T cell/ histiocyte large B-cell lymphoma treated with R-CHOP with salvage DHAP chemotherapy followed by BEAM and autologous stem cell transplant, with complete remission. Seven months post-transplant he presented with a rapidly progressive hemianopsia and aphasia, and PML was confirmed by brain biopsy. He received one dose of pembrolizumab but worsened and died of neurological deterioration secondary to PML. The third patient was a 73-year-old man with a history of mantle cell lymphoma previously treated with rituximab and bendamustine, who presented with acalculia and aphasia 14 months after rituximab exposure. PML was confirmed by brain biopsy, and he was treated with pembrolizumab with improvement in his neuro-cognitive functioning. CONCLUSION(S) We observed neurological improvement following pembrolizumab treatment for PML in two of three patients, with one patient experiencing a durable response that is ongoing 3 years following PML diagnosis.