Malignant Pleural Effusion and Advanced Stage Low-Grade Non-Hodgkin's Lymphoma Successfully Treated with Intrapleural Instillation of Rituximab

Abstract 4891

We report a patient with an advanced-stage low-grade B cell lymphoma with malignant pleural effusion. Because of the patient's age and reluctance to undergo intensive chemotherapy, we administered rituximab via an intrapleural route with the hope that it would not only control the patient's pleural effusion but the rituximab instilled in the pleural cavity would also be absorbed and would have a systemic effect to control the disease. Intrapleural rituximab therapy may be a promising treatment, not only to control the malignant pleural effusion in patients with B-cell non-Hodgkin's lymphoma (NHL), but may also be used to control the disease and help progression free survival in patients who are not willing or unable to receive intensive chemotherapy because of their age.

The patient is an 85-year-old white male who was admitted to the hospital with a history of progressive shortness of breath associated with cough, but without expectoration, and swelling of legs, lymphadenopathy and marked right sided pleural effusion. His CBC was found to be normal. A CT of the chest revealed massive right-sided pleural effusion. A CT of the abdomen and pelvis with contrast revealed a small pericardial effusion as well as extensive mesenteric and retroperitoneal lymphadenopathy. There was also bilateral inguinal lymphadenopathy. The patient underwent right inguinal lymph node biopsy, which revealed a CD 20⁺ diffuse small B cell lymphoma. Flow cytometry of the lymph node biopsy revealed CD10⁺/CD20⁺ B cell lymphoproliferative disorder. A bone marrow examination, and flow cytometry of the bone marrow aspirate revealed CD20⁺ B cell lymphoproliferative disorder. Cytogenetic analysis was normal. The patient then underwent pleurocentesis and about two liters of pleural fluid drained. The appearance of the lymphoma cells in the pleural fluid was also consistent with CD20⁺ B cell lymphoproliferative disorder. Following pleurocentesis a PleurX catheter was placed and 100 mg of rituximab in 60 ml of normal saline was instilled. The patient was then discharged home with a PleurX catheter in place and an order for the Visiting Nurses Association to drain the pleural fluid two to three times per week. Following four monthly courses of intrapleural rituximab therapy, the patient's pleural effusion resolved completely and the patient has remained effusion- and effusion related symptom-free for one year ongoing. In addition, there has also been a regression of his disease as evidenced by CT scanning.

Rituximab is a chimeric monoclonal antibody that binds to CD²⁰ antigen, which is expressed on 95 percent of the B cell lymphoma cells and on normal B cells. Conventionally, rituximab is administered almost exclusively via the intravenous route. Although the serum levels of rituximab were not measured, after intrapleural rituximab instillation, the constant, gradual reduction in the pleural effusion as well as regression of lymphadenopathy clearly demonstrate that significant amounts of the antibody were absorbed and reached the circulation in an active form to have a systemic effect. Thus, the therapeutic effect of rituximab in this case may not only be due to destruction of infiltrating lymphoma cells in the pleural cavity but also in the affected lymph nodes thus cleansing of the inguinal lymphatic drainage vessels as evidenced by regression of the patient's edematous legs. Therefore, the intrapleural instillation of rituximab may provide a novel approach not only to control malignant pleural effusions in CD20⁺ low-grade non-Hodgkin's lymphoma patients but also to treat them with a view to control the disease, improve the quality of life and afford progression free survival. We believe this is the first report of a successful use of rituximab via non-intravenous route (intrapleural) to treat a patient with CD20⁺ NHL.