Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by antibody-mediated platelet destruction and impaired platelet production, resulting in an increased risk of bleeding. In children, the annual incidence of ITP is approximately 1.9 to 6.4 per 100,000, making it the most common cause of acquired thrombocytopenia in pediatric patients. While most children achieve spontaneous remission either without treatment or following initial therapy, a subset of patients experience recurrent relapses requiring second-line interventions, including rituximab, thrombopoietin receptor agonists (TPO-RAs), splenectomy, and immunosuppressive agents. Due to the lack of prospective clinical trial data in children, selecting optimal second-line therapies remains a considerable clinical challenge.CD38 monoclonal antibodies have demonstrated favorable efficacy and safety in adult ITP patients; however, clinical evidence for their use in children remains limited.
On May 28, 2025, Dr. Lei Zhang’s team at Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences , published a study titled “Daratumumab in Relapsed or Refractory Pediatric Immune Thrombocytopenia” in The New England Journal of Medicine (impact factor 96.3). The study demonstrates that daratumumab offers both rapid onset and durable efficacy in pediatric relapsed/refractory ITP, with a favorable safety profile, providing an innovative therapeutic option for this challenging patient population.
This open-label, single-arm Phase 2 clinical trial enrolled 20 pediatric patients with persistent or chronic ITP who had previously failed guideline-recommended first-line corticosteroid therapy (due to lack of efficacy, inability to maintain response, or relapse) and at least one prior second-line therapy. Patients received daratumumab at a dose of 16 mg/kg once weekly for eight weeks. The primary objective was to evaluate the safety and efficacy of daratumumab in children with relapsed/refractory ITP.
The study found that daratumumab was generally well tolerated. The most common treatment-related adverse events were infusion-related reactions (35%) and upper respiratory tract infections (30%), which were mostly Grade 1 or 2 in severity. The most frequent infusion-related reactions included rash (15%), followed by throat discomfort (10%) and vomiting (10%). These reactions occurred primarily during the first infusion and were effectively managed through reduced infusion rates, temporary infusion interruption, or administration of premedications such as corticosteroids. One patient experienced a Grade 3 adverse event—pneumonia due to Mycoplasma infection—which resolved with timely medical intervention.
In terms of efficacy, daratumumab produced rapid and durable responses in these pediatric patients. During the 8-week treatment period, 90% of patients achieved a platelet count ≥50×10⁹/L, with a median time to first response of just one week. Subgroup analysis showed that among patients who had previously failed or relapsed after rituximab, 86% still reached platelet counts ≥50×10⁹/L within the 8-week period. Across the 24-week study period, the median cumulative duration of response for platelet counts ≥30×10⁹/L and ≥50×10⁹/L was 20.5 weeks and 19 weeks, respectively. By week 24, 50% of patients maintained a sustained response, comparable to existing second-line therapies.
This study represents the first prospective clinical evaluation of daratumumab for relapsed/refractory pediatric ITP, demonstrating multiple advantages including a high early response rate, rapid onset of action, durable efficacy, and a favorable safety profile. The findings provide important evidence supporting the use of CD38 monoclonal antibodies in pediatric ITP and offer new directions for future research and clinical practice. The widespread adoption of this novel therapeutic approach may significantly transform the treatment landscape for pediatric ITP.
References:
1. Terrell DR, Beebe LA, Vesely SK, Neas BR, Segal JB, George JN. The incidence of immune thrombocytopenic purpura in children and adults: A critical review of published reports. Am J Hematol. Mar 2010;85(3):174-80.
2. Grace RF, Shimano KA, Bhat R, et al. Second-line treatments in children with immune thrombocytopenia: Effect on platelet count and patient-centered outcomes. Am J Hematol. Jul 2019;94(7):741-750.
3. Chen Y, Xu Y, Li H, et al. A Novel Anti-CD38 Monoclonal Antibody for Treating Immune Thrombocytopenia. N Engl J Med. Jun 20 2024;390(23):2178-2190.
