Intrapleural rituximab for the treatment of malignant pleural effusion due to B-cell lymphomas

Abstract

Pleural eff usion due to lymphoma involvement is not rare, particularly in B-cell lymphoma. Th e pleural eff usion can be massive and resistant to chemotherapy treatment. Rituximab is the anti-CD20 monoclonal antibody proven eff ective for the treatment of B-cell lymphoma when given intravenously. Other routes of administration have been much less studied. Here we report our experience of the intrapleural route of administration of rituximab in controlling lymphomatous pleural eff usion for two patients with B-cell lymphoma. Th is route of administration was well tolerated, and the resolution of the eff usion suggests effi cacy of this approach in the management of resistant lymphomatous pleural eff usion. Th e fi rst patient was a 61-year-old Chinese with stage IV mantle cell lymphoma. Th ere was bone marrow and pleural involvement. Chest topography showed a massive left pleural eff usion. Th e eff usion was exudative and cytological examination showed malignant B cells (CD20 ). Smear and culture for acid-fast bacilli were negative. He was given two cycles of standard R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone) chemotherapy, but the pleural eff usion persisted and patient required frequent chest tap for relief of the compressive symptoms. At the third cycle, rituximab (100 mg in 50 mL saline as a bolus) was added and given intrapleurally after a chest tube was inserted and drained. Afterward, the chest tube was clamped for 2 h and then released. Repeat chest X-ray on day 2 showed resolving pleural eff usion (Figure 1) and further pleural tapping was not required. Th ere was no untoward side eff ect. After the fourth cycle of R-CHOP, the patient had lymphoma progression with central nervous system involvement. Further salvage chemotherapy including high-dose methotrexate and cytarabine was given. Th e lymphoma did not respond. Despite this, there was no recurrence of the pleural eff usion. Th e second patient was a 44-year-old man suff ering from marginal zone B-cell lymphoma. He presented with left supraclavicular lymph node involvement and left massive pleural eff usion. Pleural eff usion was exudative and biopsy showed atypical lymphoid infi ltrates. Immunophenotyping study confi rmed malignant B cell (CD20 ) involvement. Computed tomography of the thorax and the abdomen showed extensive thoracic and abdominal lymph node diseases and the pleural eff usion. Th e bone marrow was not involved. Two cycles of R-CHOP chemotherapy at standard dosing were given, but there was persistent signifi cant eff usion that required repeated chest drainage. Th ere was rapid re-accumulation of the pleural fl uid after the chest tube was removed. In view of the inadequacy of systemic chemotherapy in controlling the pleural eff usion, rituximab (50 mg in 50 mL saline as a bolus) was administered intrapleurally together with the fi rst day of intravenous chemotherapy and rituximab at the third cycle. Two more doses of rituximab (100 mg in 50 mL saline) were given intrapleurally 3 weeks apart in subsequent cycles. Th e patient tolerated the intrapleural rituximab and the eff usion subsided gradually. A total of eight cycles of systemic chemotherapy was given, and complete remission was achieved. Malignant pleural eff usion is a common problem in patients suff ering from neoplastic diseases, and about 10% of such cases are attributed to non-Hodgkin lymphoma [1]. Tumor infi ltration of the parietal or visceral pleura, or blockage of lymphatic drainage by the tumor or neoplastic lymph nodes, leads to pleural eff usion. Systemic chemotherapy can be eff ective in controlling the pleural eff usion. When systemic therapy fails, local therapy has to be considered. In our two patients with mantle cell lymphoma and marginal zone B-cell lymphoma, there was persistent pleural eff usion after standard cycles of systemic chemotherapy and intravenous rituximab. Th e eff usion resolved after the subsequent addition of rituximab given through the intrapleural route. Although intravenous rituximab and chemotherapy has been the standard of care for most patients suff ering from B-cell lymphoma, the intravenous route may not deliver suffi cient quantity of the anti-CD20 antibody to act on the lymphoma cells present in the pleural cavity. Th e intrapleural route might allow achievement of a high enough concentration of the antibody for lymphoma cell kill in the pleural cavity. Th e therapeutic eff ect of intrapleural rituximab may also be due to the destruction of infi ltrating lymphoma cells