The commentary “Daratumumab in Children with Advanced Idiopathic Thrombocytopenic Purpura”, written by Robert Peter Gale (Imperial College London; Peking University People’s Hospital; Sun Yat-sen Cancer Centre), was published in Blood Science (2025, Vol. 7, e00245) by the Chinese Medical Association and the Institute of Hematology, Chinese Academy of Medical Sciences. The article reviews a groundbreaking Phase II trial conducted by Sun et al. (2025) in Tianjin, China, demonstrating the safety and efficacy of daratumumab for pediatric patients with refractory immune thrombocytopenic purpura (ITP).Background
Idiopathic thrombocytopenic purpura (ITP) is an autoimmune disorder characterized by low platelet counts due to antibody-mediated destruction and impaired platelet production. Although most children respond to first-line treatments such as corticosteroids, IV immunoglobulin (IVIG), or anti-D therapy, some relapse or fail to respond, progressing to chronic or refractory ITP.
Second-line options—such as rituximab (anti-CD20), immunosuppressants, splenectomy, and thrombopoietin receptor agonists (TPO-RAs) like eltrombopag, romiplostim, or hetrombopag—can induce remission but are often followed by relapse. More recently, umbilical cord–derived mesenchymal stromal cells have shown partial success, yet long-term remission remains elusive.
The Tianjin Study
In this context, Sun and colleagues from the National Clinical Research Center for Blood Diseases and the State Key Laboratory of Experimental Hematology, Tianjin, conducted a Phase II clinical study involving 20 children with advanced ITP who had failed multiple prior treatments.
Participants received daratumumab, an anti-CD38 monoclonal antibody that targets plasma cells responsible for autoantibody production. Originally developed for multiple myeloma, daratumumab has demonstrated potent immunomodulatory effects by depleting pathogenic plasma cells.
Results were remarkable:
- 18 of 20 children (90%) achieved platelet responses within 8 weeks.
- The median time to response was 1 week (interquartile range: 1–2 weeks).
- 17 of 18 responders had previously failed rituximab therapy.
Treatment was well tolerated, with no serious adverse events or unexpected toxicities reported. These findings position daratumumab as a potential new therapy for refractory pediatric ITP.
Commentary and Insights
Gale highlights several striking aspects of the study. The speed of platelet recovery—often within days of therapy—is surprising given the approximately three-week half-life of IgG, which suggests that mechanisms beyond simple antibody clearance are at play. Possible explanations include rapid immune modulation or plasma-cell depletion affecting autoreactive B-cell networks.
He also emphasizes the need to clarify how long responses last and whether maintenance therapy might be required. The durability of remission and long-term immunologic consequences of plasma-cell depletion remain unknown.
Furthermore, Gale speculates that bi-specific antibodies or anti–BCMA (B-cell maturation antigen) CAR-T cells may offer even more sustained benefits for refractory autoimmune thrombocytopenia in the future.
Clinical Implications and Future Perspectives
The Tianjin study represents a major therapeutic advance for children with chronic or refractory ITP. If validated in larger, multicenter trials, daratumumab could become an effective second- or third-line option for patients unresponsive to rituximab or TPO-RAs.
Its rapid onset, favorable safety profile, and potential for durable remission mark an important step forward in immune-targeted pediatric hematology. However, long-term follow-up is essential to assess relapse risk, infection susceptibility, and immune reconstitution post-treatment.
Conclusion
The Phase II data from Sun et al. provide compelling early evidence that daratumumab is a safe and effective therapy for children with advanced, treatment-resistant ITP. As emphasized by Robert Peter Gale, these results are promising but require confirmation in larger studies. If reproduced, daratumumab could redefine management strategies for pediatric autoimmune thrombocytopenia, offering renewed hope to patients with few remaining options.
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