Outcomes 5 years after response to rituximab therapy in children and adults with immune thrombocytopenia

Abstract

Treatments for immune thrombocytopenic purpura (ITP) providing durable platelet responses without continued dosing are limited. Whereas complete responses (CRs) to B-cell depletion in ITP usually last for 1 year in adults, partial responses (PRs) are less durable. Comparable data do not exist for children and 5-year outcomes are unavailable. Patients with ITP treated with rituximab who achieved CRs and PRs (platelets > 150 × 10(9)/L or 50-150 × 10(9)/L, respectively) were selected to be assessed for duration of their response; 72 adults whose response lasted at least 1 year and 66 children with response of any duration were included. Patients had baseline platelet counts < 30 × 10(9)/L; 95% had ITP of > 6 months in duration. Adults and children each had initial overall response rates of 57% and similar 5-year estimates of persisting response (21% and 26%, respectively). Children did not relapse after 2 years from initial treatment whereas adults did. Initial CR and prolonged B-cell depletion predicted sustained responses whereas prior splenectomy, age, sex, and duration of ITP did not. No novel or substantial long-term clinical toxicity was observed. In summary, 21% to 26% of adults and children with chronic ITP treated with standard-dose rituximab maintained a treatment-free response for at least 5 years without major toxicity. These results can inform clinical decision-making.

Figure 1

Long-term response rates in adults and children treated with rituximab: estimates incorporating published reports and data from this report. Shaded ovals represent data derived from published reports (Table 1). Open ovals represent data presented in this report.

Figure 2

Response duration in all children who responded to rituximab (however transiently) and adults whose response lasted at least 1 year since treatment. Kaplan-Meier estimates of response to rituximab past 1 year in (A) children (n = 38) and (B) adults (n = 72). Vertical lines along the Kaplan-Meier curve indicate the last follow-up of an ongoing response. Adult long-term response rate projection originated at 1 year, 38%, based on published reports (Figure 1). Children's long-term response rate projection originated at 1 year, 33%, based on published reports and data presented in this study (gray line; Figure 1). Error bars (dotted lines) represent the 95% confidence intervals of response projections.

Figure 3

B-cell repopulation after rituximab infusion in ITP patients with initial response > 1 year. Solid lines denote patients who relapsed after 1 year (n = 14), and dashed lines denote patients responding over 2.5 years without relapse (n = 18). Linear functions describing the mean rate of B-cell return in individual patients were used to calculate the average linear rate of B-cell return in those who relapsed (solid line) and in responders > 2.5 years (dashed line); dotted lines represent the SEM of these linear functions (P < .05). Curved solid and dashed trendlines represent the spline fit of the average number of CD19⁺ B cells (×10⁹/L) in patients who relapsed after 1 year and those responding over 2.5 years (measured at 50-day intervals), respectively; curved trendlines were not used for statistical determinations.