1Yousef Saleh Aldughaythir, 1Mazen Sulaiman Alamr
1King Fahad Medical City, Riyadh, Saudi Arabia
Progressive multifocal leukoencephalopathy (PML) is a fatal, rare viral infection of the brain that leads to demyelination and neuronal loss. It develops almost exclusively in patients with a compromised cell-mediated immunity with conditions like acquired immunodeficiency syndrome, hematologic malignancies and treatment with immunosuppression. No treatment is available to reveres or halt the progression of the disease. Pembrolizumab is a monoclonal antibody to programmed cell death-1 (PD-1) protein, inhibiting PD-1 activity allows proliferation of T-cells and enhancing the immune function. Few studies reported the use of pembrolizumab in patients with PML which showed variable response in restoring immune function and halting disease progression.
Material(s) and Method(s):
A single dose of pembrolizumab 2 mg/kg was administered to a patient with PML secondary to treatment of diffuse large B-cell lymphoma. She completed 6 cycles of R-CHOP therapy (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), and presented 6 months later with progressive neurologic symptoms of behavioral changes, dysarthria, gait difficulty and left sided weakness. MRI brain reveled asymmetric, confluent, non-enhancing bifrontal white matter T2/FLAIR lesions with no mass effect, edema and no diffusion restriction. PCR of cerebrospinal fluid confirmed the presence of JC virus DNA.
Five weeks following administration of pembrolizumab, her neurologic status deteriorated, she was not producing words, not following commands, developed dysphagia, spastic quadriplegia and generalized seizures. Eventually she was pronouncing dead due to asystole.
The unfortunate rapid progression of the disease in this patient prevented the planned treatment regimen of 3 doses separated by 6 weeks. We are hoping that this case will encourage further investigation into this untreatable fatal disease.