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

Fibrosing mediastinitis is an uncommon fibro-inflammatory 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. To evaluate the benefits and side effects of Rituximab in patients with progressive and symptomatic fibrosing mediastinitis. We treated 22 patients (median age 35 years, range: 15-68 years, 45% female) with metabolically active, progressive fibrosing mediastinitis with off-label rituximab. Additionally, patients were put on 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; time-to-event modeling was performed to estimate treatment response rates based on a >30% reduction in pre-treatment volume. The primary end points were lack of disease progression and change in mediastinal lesion volume by CT (evaluated retrospectively). No patient experienced disease progression after rituximab therapy. Median clinical follow-up was 42 months (range: 7 to 94) and imaging follow-up 21 months (range: 7 to 62). 82% of patients had confirmed histoplasmosis-associated fibrosing mediastinitis. After rituximab treatment a 49.6% (95% CI = [17.5%, 64.4%]) mean estimated decrease in pre-treatment lesion volume was observed at 24 months. The estimated objective treatment response rate was 47.9% (95% CI = [26.7%, 70.3%]). This observational study suggests that Rituximab is well tolerated and potentially effective therapy in a cohort of patients with symptomatic and progressive FM.