Prospective phase 1/2 study of rituximab in childhood and adolescent chronic immune thrombocytopenic purpura

Abstract

We assessed safety and efficacy of rituximab in a prospective study of 36 patients, age 2.6 to 18.3 years, with severe chronic immune thrombocytopenic purpura (ITP). The primary outcome of sustained platelets above 50 x 10(9)/L (50,000/mm3) during 4 consecutive weeks, starting in weeks 9 to 12, was achieved by 11 of 36 patients (31%, confidence interval [CI], 16% to 48%). Median response time was 1 week (range, 1 to 7 weeks). Attainment of the primary outcome was not associated with age, prior pharmacologic responses, prior splenectomy, ITP duration, screening platelet count, refractoriness, or IgM reduction. First-dose, infusion-related toxicity was common (47%) despite premedication. Significant drug-related toxicities included third-dose hypotension (n = 1) and serum sickness (n = 2). Peripheral B cells were depleted in all subjects. IgM decreased 3.4% per week, but IgG did not significantly decrease. Rituximab was well tolerated, with manageable infusion-related side effects, but 6% of subjects developed serum sickness. Rituximab is beneficial for some pediatric patients with severe, chronic ITP.

Figure 1.

Platelet response to rituximab. Boxplot of platelet counts (on log scale) over time in weeks for responders (gray) and nonresponders (white) from weeks 0 through 16. The first rituximab dose was administered in week 1. The broken horizontal line represents the primary outcome platelet count of 50 × 10⁹/L (50 000/mm³). The horizontal lines in each plot, from highest to lowest, represent the 90th, 75th, 50th (median), 25th, and 10th percentiles.