Comparison of Time to Relapse between Low-Fixed Dose Versus Standard-Dose Rituximab in the Treatment of ITP, TTP, and AIHA

Abstract

Background: The optimal Rituximab dosing regimen for the treatment of immune thrombocytopenia purpura (ITP), autoimmune hemolytic anemia (AIHA), or thrombotic thrombocytopenia purpura (TTP) has not been well established. To our knowledge, there has not been a randomized trial examining the time to relapse with the different Rituximab dosing regimens (low-fixed dose of 100 mg x 4 weekly doses versus standard dose of 375 mg/m2 x 4 weekly doses) in the treatment of ITP, TTP, and AIHA. Previous comparative studies have shown that the weekly low-fixed Rituximab dosing regimen has been shown to be just as effective in treating these diseases as demonstrated by similar response and duration of response. Therefore, we conducted a comparative analysis to evaluate the time to first recurrence after being treated with Rituximab. Methods: We collected clinical data from a single center of patients with diagnosis of ITP, TTP, or AIHA and were treated with 4 weekly low-fixed or standard dose Rituximab. Time to first recurrence was measured to compare if there was a significant difference between the two Rituximab dosing regimens. Kaplan-Meier time to recurrence estimates were used to generate time to recurrence curves. Results: Of the 30 patients analyzed, 10 patients were diagnosed with AIHA, 12 patients with ITP, and 8 with TTP. All patients had a complete response (CR) per the specific disease CR definition prior to first disease recurrence. 17 patients were treated with standard dose Rituximab and 13 patients were treated with low-fixed dose Rituximab. 17 patients did not have a recurrence in the selected time frame of the study. Recurrence was observed in 40% of the AIHA patients, 50% of the TTP patients, and 37.5% of TTP (P=0.8297). 47% females had a recurrence compared to 36% males (P=0.7084). Recurrence was observed in 61% patients who received the low-fixed dose Rituximab and 29% of patients who received the standard dose Rituximab (P=0.1376). The median time of recurrence was 16 and 27 months among patients who received low-fixed dose vs standard dose Rituximab, respectively (P=0.1914). Conclusions: The use of low-fixed dose Rituximab versus standard dose Rituximab for treatment of ITP, TTP, and AIHA appears to have a higher recurrence rate but did not meet statistical significance. The median time difference in recurrence was 9 months. This could potentially be significant in a larger study population. Further investigation through large, randomized controlled trials is needed to assess if there is a significant difference in recurrence rate and time to recurrence between the two Rituximab dosing regimens.