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

BACKGROUND: 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. OBJECTIVE: We aimed to evaluate the real-world effectiveness of PyVST in patients with PML. METHODS: We retrospectively analyzed 64 patients from 13 centers who received PyVST alongside standard care. RESULTS: 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 3-4] vs. 4 [IQR 4-5], p=0.0317) and lower cerebrospinal fluid (CSF) JCPyV DNA (3.03 [IQR 2.66-3.47] vs. 4.29 [IQR 3.31-4.79] log₁₀ copies/mL, p=0.0037) compared to non survivors. In multivariate analysis performed on 38 patients with complete data, only CSF JCPyV DNA level was associated with survival (p=0.0266). 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%). CONCLUSIONS: In this uncontrolled analysis, adoptive T cell therapy yielded encouraging one-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.