Intrapleural Rituximab (R) Is Effective in Refractory Pleural Effusion Due to Non- Hodgkin’s Lymphoma

We report the case of a 65 years old woman with a NHL, CD20 +, BCL-2 negative, Grade III, CS: IVBX, FLIPI High Risk, diagnosed on September 2005. The patient was treated with several chemotherapy regimens (CHOP, chlorambucil/prednisone, cyclophosphamide/prednisone), while on treatment a large pleural effusion was found on a chest X-ray. On pleural fluid cytology we observed numerous abnormal lymphocytes. We did repeated thoracocentesis without success, finally a pleural tube was inserted and intrapleural bleomycin instilled, again with no success (Table 1). Six weeks later, after signing informed consent, we administered 50 mg of intrapleural R (50 mg in 50 cc of SS 0.9%) without immediate or delayed adverse events. On day +4 a new chest X-ray showed marked improvement. We planned to repeat the dose every week × 4, unfortunately the patient could not afford it. After seven months the patient is asymptomatic and without recurrence of the pleural effusion. Table 1 Date (2007) Fluid drained (ml) Action September 12 Dyspnea September 21 1,500 October 4 1,500 October 6 570 October 8 400 October 12 20 Bleomycin 10 U November 6 Dyspnea/1,300 November 9 40 November 16 400 November 17 200 November 20 100 Rituximab 50 mg Discussion Although the pharmacology of IV R is welll known, there is scarce information about dosage, penetration into the tissues and efficacy of intracavitary R. It is likely that the intrapleural instillation of R was effective in the control of this complication in a definitive way, without adverse effects, Our case supports the results reported by Schmidt et al (Table 2). The mechanism of action at the local site is not known, but it could be the same as described with the systemic use. Pleural effusion secondary to refractory lymphoma is a rare complication, we propose the integration of an international registry of this cases to study the pharmacokinetics, pharmacodynamics, efficacy and safety of intrapleural rituximab. Table 2 Features Our patient Schmidt Patient Age age 65 years 57 years Diagnosis Follicular NHL, Grado II Lymphoplasmacytic NHL No. Previous Therapy 3 1 Effusion therapy Thoracocentesis and drainage by pleurostomy Thoracocentesis Rituximab Dose 50mg, single dose 50mg day 1 200mg day 2 400mg day 3 Time to Response 4 days 3 days