Can Rituximab Replace Splenectomy in Immune Thrombocytopenic Purpura (ITP)?.

Introduction: Immune thrombocytopenia purpura (ITP) is an autoimmune disorder characterized by premature platelet destruction by the reticuloendothelial system, mediated by autoantobodies against platelet antigens. The main goal of treatment is to provide a safe platelet count to prevent major bleeding. Current practice is to initiate treatment with corticosteroids, followed by splenectomy as the traditional second-line. Relapses still occur in a third of these patients, and splenectomy is associated with approximately 1 percent operative mortality and lifelong increased risk of opportunistic infections. Rituximab, a monoclonal antibody targeting the CD20 surface antigen on the B-lymphocytes, has shown major responses (platelet counts >50,000/microL) in approximately 50 percent, with complete remissions (CR) (platelet counts >150,000/microL) in about one-third. Although clearly a useful agent in ITP, published data is sparse; available literature is in patients with chronic refractory ITP having failed multiple prior treatments, including splenectomy. While two systematic reviews of case series in patients with chronic refractory ITP, have documented a 30 to 43 percent CR rate, the median follow-up was only 9.5 months, thereby questioning the durability of these responses. We therefore attempted to analyze our ITP patients treated with rituximab prior to splenectomy.

Study: A retrospective chart review of patients with ITP treated with rituximab between January 2001 and December 2006 was carried out. Data included age, sex, date of diagnosis, previous treatments including splenectomy, platelet counts before and after treatment with rituximab, type and duration of response, and date of relapse, last follow up or death. Rituximab was administered as a weekly infusion of 375 mg/m2 for 4 consecutive weeks. We defined CR as a platelet count greater than 150 x 10^9 cell/l and partial response (PR) as between 50 and 150x10^9 provided response was sustained for 12 months.

Results: A total of 29 patients were treated with rituximab in the second line setting. Eighteen (62%) had a CR, 2 (7%) had a PR, with an overall response rate (ORR) of 69%, but 6 (21%) did not respond. The average time to response was 5 weeks. An additional 3 (10%) achieved a CR which was short lived, and they had to be treated with other modalities. Neither did age, race, sex or steroid responsiveness predict response to treatment. Of note, however, amongst those who responded, majority had received rituximab soon after their diagnosis, usually within a year.

Conclusions: Our study demonstrated higher CR rates to those published, with longer duration of response. This could be due to the fact that our patients received rituximab earlier in the course of their disease. We believe it underscores such a use for the drug, and would support future clinical trials like the one in Norway, prospectively looking to determine whether early treatment with Rituximab can result in durable remissions, and lead to the avoidance of splenectomy in a significant number of patients. We conclude that rituximab is an effective second line option in ITP treatment, achieving higher long lasting response rates with minimal toxicity, thereby avoiding the need for splenectomy in a majority.