Long-Term Follow-up of Rituximab Treatment of Non-Familial Idiopathic Thrombotic Thrombocytopenic Purpura (TTP).

Rituximab is an accepted treatment modality for patients with TTP refractory to plasma exchange or recurrent disease. While initial treatment response rates are at a high level, long-term follow-up of patients treated with Rituximab is not accessible to date. However this data implies important information, since overall and progression free survival, side effects and a possible need for a maintenance therapy must be taken in consideration.

12 patients with TTP refractory to plasma exchange or with recurrent disease treated with Rituximab at the haematology department of the University of Cologne between 2000 and 2008 were re-examined. All patients suffered from non-familial idiopathic TTP, cases with secondary TTP following stem cell transplantation or underlying diseases such as cancer or rheumatologic disorders were excluded. Additional to physical examination, ADAMTS13 activity and the presence of an ADAMTS13 inhibitor were analyzed.

The median age of the patients was 43.2 years and 75% of the patients were female. The majority of patients received Rituximab either because of refractory disease or severe allergic reactions during standard therapy with plasma exchange. 4 patients suffered from relapsing disease after standard therapy with plasma exchange during the first episode. Dose schedule of Rituximab treatment consisted of 4 times 375 mg/m² per week in parallel to continuing plasma exchange when possible. No acute severe side effects were seen after application of Rituximab. The median follow-up was 48.8 months, ranging from 10 to 98 months. All patients had an initial complete response after Rituximab treatment. At the time of re-examination, all 12 patients presented in good clinical condition, thus overall survival accounted 100%. 10 patients remained long-term disease free after initial therapy with Rituximab, two patients had recurrent disease but responded to subsequent Rituximab treatment. One patient is treated with ongoing maintenance therapy with Rituximab consisting of 375 mg/m² every 4 weeks and remains disease free under these conditions. In our patient cohort, no long-term side effects of Rituximab treatment were noted. ADAMTS13 enzyme activity at time of re-evaluation was impaired in 50% of the patients, however no patient had an enzyme activity of less then 5%. Inhibitors against ADAMTS13 at time of re-evaluation were detected in three patients.

Rituximab is a safe and effective treatment for patients with non-familial idiopathic TTP after failure of standard therapy with plasma exchange. More than 80% of patients remain disease free during long-term follow-up, and relapses can be treated with subsequent Rituximab. Maintenance therapy is an option for frequent relapsing patients. ADAMTS13 activity might be reasonable to analyze on a regular basis to identify patients who benefit from pre-emptive Rituximab treatment.

No relevant conflicts of interest to declare.