Prolonged survival in HIV-associated Progressive Multifocal Leukoencephalopathy treated with Pembrolizumab: a case series on treatment and long-term follow-up

• DOI: 10.1007/s13365-025-01243-0
• Publication Date: 2025-02-19T18:56:26Z
• Authors: Marta Chiuchiarelli; Giulia Micheli; Francesco Vladimi...; Gabriele Giuliano; Paola Del Giacomo; Alex Dusina; Elena Matteini; Federico Frondizi; Simona Gaudino; Francesca Lisi; Eleonora Cimini; Rosaria Santangelo; Chiara Agrati; Carlo Torti; Antonella Cingolani

Abstract Progressive Multifocal Leukoencephalopathy (PML) is a rare opportunistic infection of the central nervous system (CNS) caused by human polyomavirus JC virus, with high mortality rate in people living with HIV (PLWH), without an effective specific treatment beside combined antiretroviral therapy (cART). The use of Pembrolizumab, an inhibitor of the Programmed cell death protein 1 (PD-1) receptor on T cells, has been associated with decreased viral clearance. Aim of this study is to evaluate clinical course of PLWH affected by PML treated with pembrolizumab. We report four consecutive PLWH with clinical and radiological evidence of PML and JCV-DNA detection in cerebrospinal fluid (CSF). Pembrolizumab was administered to all four PLWH alongside cART. Radiological and laboratory follow-up were performed at the end of the medical protocol. Clinically, 3 out of 4 PLWH showed an improvement in neurological deficits, partially reacquiring the lost functions, and they are alive at 3.5 years, 14 months, and 9 months, respectively; the fourth patient died shortly after treatment due to worsening respiratory conditions. In all the PLWH completing treatment, a decrease of about 80–90% of the specific PD-1 activity was observed. Prolonged survival and stabilization of radiological findings have been observed, along with clinical improvement and partial recovery of acquired deficits in 3 out of 4 PLWH. In addition, a decrease in anti-PD-1 expression has also been observed, suggesting a link between the therapy and the success achieved. Given the small sample and conflicting evidence in the existing literature, further investigation is needed to assess its effectiveness.