Rituximab Treatment Affords Long Term Control in Thrombotic Thrombocytopenic Purpura (TTP): The University of Kansas Experience.
Authors: Thirunavu Meenakshi , Deauna-Limayo Delva , Patel Jigar , Bodensteiner David C. , Skikne Barry S. , Ganguly Siddhartha S. , Lacy Norma , Sahud Mervyn A. 
Published: April 2020

Abstract
The discovery that acquired TTP results from autoantibodies to ADAMTS-13, a von Willebrand factor-cleavage protein (vWF-CP), provided rationale for rituximab immunosuppression as an adjunct treatment. We previously reported our experience with 5 refractory TTP patients treated with rituximab (Ann Hematology 2005, 84:232). Rituximab was administered at 375 mg/m2 IV weekly for 4 weeks. Therapeutic plasma exchanges (TPE) were held at least 24 hours post rituximab. All patients attained durable remissions with a median response of 15 months (range: 10–21). Literature review revealed 11 other studies reporting longest response duration of 23 months. Since our initial report, we treated 5 additional patients with TTP: 1 refractory and 4 newly diagnosed. Of the previously reported 5 patients with refractory TTP, 3 were female and 2 were male patients with a median age of 37 years (27–70). All patients achieved complete responses (CR). The median duration of response has increased to 32 months with a follow up period of 25 to 51 months. The longest response has been sustained 44 months after the first dose of rituximab. One patient developed clinical relapse after 26 disease-free months. She achieved CR2 after another 4 doses of rituximab with continued response 12 months after re-treatment. Time to response was shorter with re-treatment, 4 weeks vs. 5 weeks at initial therapy. Our first male patient with refractory TTP who was treated in 4/02 remained in remission for 25 months until his death from unrelated causes. One additional male patient with refractory TTP was treated preemptively due to recurrent loss of vWF-CP activity after achieving initial response with TPE and steroids. Treatment resulted in reappearance of vWF-CP activity, with continued response 30 months from first dose of rituximab. Four newly diagnosed female patients were treated: 3 had idiopathic TTP, and 1 had associated SLE. Median age was 20 years (range: 16–30). The cohort had a median platelet count of 28×109/L (range: 11–56), median hemoglobin of 10g/dL (range: 6–12) and a median lactate dehydrogenase of 868 IU/L (range: 618–1737). The median TPE’s received prior to rituximab therapy was 6 (range: 4–9) and after initiation of rituximab was 17 (range: 12–19). All patients achieved CR with median time to response of 4.5 weeks (range: 3–8). Responses are maintained 13 to 27 months after initial rituximab dose. The patient with SLE attained a complete clinical response but developed persistently low platelets unrelated to her TTP. Among the 10 patients treated, decreased or absent vWF-CP activity with presence of inhibitor were noted in 6 patients, 3 had normal levels and 1 was not tested. Our experience suggests that rituximab is safe and effective in TTP patients with refractory and newly diagnosed disease. Time to response was similar among refractory and newly diagnosed patients. To our knowledge, 44 months is the longest remission duration reported in the literature among refractory TTP patients treated with rituximab. Extended follow up is necessary to determine durable remissions among patients with newly diagnosed disease.