A Retrospective Evaluation of the Treatment Effects of Rituximab in Patients with Progressive and Symptomatic Fibrosing Mediastinitis.

Rationale: Fibrosing mediastinitis (FM) is an uncommon fibroinflammatory condition without established or effective medical therapies. Infiltrating B lymphocytes are commonly present, and progressive fibrosis compromises mediastinal structures, including blood vessels and airways, resulting in significant morbidity and mortality. Objective: To evaluate the benefits and side effects of rituximab in patients with progressive and symptomatic FM. Methods: We treated 22 patients (median age, 35 yr; range, 15-68 yr; 45% female) with metabolically active, progressive FM with rituximab on an off-label basis. Additionally, patients were administered pneumocystis and antifungal prophylaxis when immunosuppressed with rituximab. Modeling of longitudinal treatment response based on changes in relative lesion volume from baseline was performed retrospectively using functional data analysis, and time-to-event modeling was performed to estimate treatment response rates based on a >30% reduction in pretreatment volume. The primary endpoints were lack of disease progression and change in mediastinal lesion volume on computed tomography (evaluated retrospectively). Results: No patient experienced disease progression after rituximab therapy. Median clinical follow-up was 42 months (range, 7-94 mo) and imaging follow-up 21 months (range, 7-62 mo). A total of 82% of patients had confirmed histoplasmosis-associated FM. After rituximab treatment, a 49.6% (95% confidence interval, 17.5-64.4%) mean estimated decrease in pretreatment lesion volume was observed at 24 months. The estimated objective treatment response rate was 47.9% (95% confidence interval, 26.7-70.3%). Conclusions: This observational study suggests that rituximab is a well tolerated and potentially effective therapy in a cohort of patients with symptomatic and progressive FM.