Polyomavirus-Specific T Cells in Progressive Multifocal Leukoencephalopathy: A Multicenter Retrospective Analysis

Progressive multifocal leukoencephalopathy (PML) is a rare brain infection caused by JC polyomavirus (JCPyV) in immunocompromised individuals, for which no effective antiviral therapy exists. Diverse cellular therapy approaches using polyomavirus-specific T cells (PyVST) has emerged as a therapeutic option. We aimed to evaluate the real-world effectiveness of PyVST in patients with PML. We retrospectively analyzed 64 patients from 13 centers who received PyVST alongside standard care. Conditions predisposing to PML included mainly hematologic malignancies (33/64, 51.6%). One-year survival was 62% (36/58) when excluding patients whose deaths were unrelated to PML. Most patients received BK virus-specific T cells (55/64, 84.6%), isolated mainly via Interferon-γ capture system (37/64, 57.8%), and from related donors (32/64, 50%). At therapy initiation, survivors had lower modified Rankin scale (3 [IQR 3 to 4] versus 4 [IQR 4 to 5], P = .0317) and lower cerebrospinal fluid (CSF) JCPyV DNA (3.03 [IQR 2.66 to 3.47] versus 4.29 [IQR 3.31 to 4.79] log₁₀ copies/mL, P = .0037) compared to non survivors. In multivariate analysis performed on 38 patients with complete data, only CSF JCPyV DNA level was associated with survival (P = .0266). No manufacturing characteristic or HLA-matching were associated with outcome. Adverse events were rare, with PML-associated immune reconstitution inflammatory syndrome reported in 5/64 patients (7.8%) and rash in 2/64 patients (3.1%). In this uncontrolled analysis, adoptive T cell therapy yielded encouraging 1-year survival rates in patients with PML and demonstrated a favorable safety profile. Important questions remain regarding the optimal strategy for T-cell generation, as well as the specific product and recipient characteristics most likely to influence treatment outcomes.