Dose dense rituximab for high-risk children and adolescents with newly diagnosed acute immune thrombocytopenic purpura (ITP) (NCT04323748) Free

Background: Immune thrombocytopenic purpura (ITP) is an immune-mediated bleeding disorder, occurring mainly in young children, with an overall incidence of 4–5/100,000 per year. ITP is classified into acute and chronic forms, with chronic ITP occurring in 35% of cases. Numerous studies have investigated biomarkers such as platelets (PLT) antibodies, and regulatory T cell ratio, but none are reliable predictors for chronicity. B cells have a well-established role in ITP pathogenesis, as they are the source of antibodies directed against platelet-surface glycoproteins. Rituximab (RITUX), a monoclonal antibody directed against CD20, a glycoprotein expressed on the surface of B cells, leads to a fast and thorough, but reversible B-cell depletion. Chugh et al. (2015, Lancet) conducted a systematic review and meta-analysis of randomized controlled trials that evaluated the efficacy and safety of rituximab in adults with primary ITP. Complete response (CR), defined as platelet count >100×10⁹/L without rescue therapy, was more common with rituximab than with standard of care (weighted proportions: 46.8% vs 32.5%; relative risk [RR] 1.42, 95% CI 1.13–1.77; p=0.002). However, there is a paucity of data on the safety, efficacy, and optimal dosing of RITUX in newly diagnosed pediatric ITP. While existing therapies provide temporary effect on platelets counts, we hypothesized that dose dense RITUX would be safe to use in newly diagnosed ITP and will reduce chronicity rates.

Objective: To assess the safety and efficacy of dose dense RITUX in high risk newly diagnosed pediatric ITP patients.

Design/Methods: Patients with acute ITP, ages 0.5 to 21 years of age, with a PLT count ≤ 20x10⁹/L and high-risk features such as need for hospitalization were enrolled. Study includes 2 arms: RITUX upfront and a control arm. Eligibility criteria for RITUX arm included: performance status ≥50%, no prior ITP therapy and adequate renal and liver function. The control arm included patients with similar inclusion criteria, who were treated at Maria Fareri Children's Hospital (MFCH), NY, USA, between the years 2019-2025. IV RITUX was administered at 375mg/m²/dose within 24 hours of consent and again on days: 2, 7, 14, and 21. On the control arm patients were either observed without intervention or treated with steroids and/or IVIG. Complete blood counts of patients were taken at various time points and again on day 180 post initial therapy. CR was defined as PLT count ≥ 100x10⁹/L without recent additional ITP directed therapy in the month prior. Days to CR were compared using a Log-rank (Mantel-Cox) calculation using the Prism program, and continuous complete response rate (CCR) by Chi-Square test with Excel. Adverse events (AEs) were defined based on chart review on the control arm or as reported by the investigator on the RITUX arm.

Results: Between July 2019 to February 2025, 48 patients presented to MFCH with newly diagnosed ITP and met our inclusion criteria. All patients had at least 6 months follow up post ITP diagnosis. Only 8 of those were enrolled on our RITUX arm, ages 1.9-14 years old (median 4.5 years), and a Male/Female ratio of 7/1. The 40 remaining patients, ages 0.5-19 years old (median 5 years), and M/F ratio of 19/21 were included in our control arm. The mean PLT count at diagnosis was 4.8x10⁹/L on the control arm and 6.1x10⁹/L on the RITUX arm. On the control arm, all patients but two were treated with IVIG (95%), and 28 patients (70%) received a concurrent course of steroids as part of their initial therapy. Most common AEs included epistaxis (28%), headaches (20%) and emesis (15%) on the control arm, with 13% having similar AEs on the RITUX arm. No significant grade III/IV AEs were recorded in both arms. Among those achieving CR on the control arm, the average time to CR was 16.7 days (range: 2-88 days), and only 67.5% of patients on control arm achieved CCR at 6 months post ITP diagnosis. In comparison, on the RITUX arm, the average time to CR was 20 days (range 2-53 days), and all patients were in CCR at 6 months post diagnosis. No difference was observed between time to CR between both arms (p=0.552), however, a trend towards significant difference between CCR (p=0.059) was observed.

Conclusions: Dose dense RITUX appears safe and may be considered for newly diagnosed pediatric ITP. Trends indicate improved CCR rates and fewer AEs in the RITUX arm. Accrual is ongoing.