Daratumumab in patients with immune thrombocytopenia: a single-center, open-label, phase 2 trial.

Abstract

Immune thrombocytopenia is an autoimmune bleeding disorder. Daratumumab, a human monoclonal antibody targeting CD38 glycoprotein, is currently under clinical investigation as a potential therapy for autoimmune diseases. This trial aimed to evaluate the efficacy and safety of daratumumab in adults with immune thrombocytopenia. This single-center, open-label, phase 2 trial enrolled patients with a platelet count <30 × 10⁹ platelets per L during the screening period. The study protocol comprised a 4-week screening phase, an 8-week treatment course, and a 16-week follow-up period. Daratumumab was administered intravenously at 16 mg/kg once weekly for eight consecutive weeks. The primary endpoint was defined as two or more consecutive platelet counts of at least 50 × 10⁹ platelets per L within 8 weeks. This trial is registered at clinicaltrials.gov as #NCT05562882. Between December 10, 2022, and August 15, 2024, 63 patients were enrolled. All participants completed the full treatment and follow-up schedule. 52 patients (83%) reached the primary endpoint, with 46 (73%) having platelet counts of at least 50 × 10⁹ platelets per L within the first week. At week 8, 49 patients (78%) had an overall response, including a complete response in 32 (51%). An overall response was observed in 38 patients (60%) at week 24. The proportion of patients with bleeding symptoms (WHO grade 1-4) declined from 44% (28 of 63) at baseline to 10% (6 of 63) at week 8. Infusion-related reactions were reported in 32% (20 of 63) of cases, primarily during the initial administration. Infections occurred in 32% (20 of 63) of patients, with upper respiratory tract infections accounting for 24% (15 of 63). These findings suggest that daratumumab could be a potential therapeutic option for adults with immune thrombocytopenia, with observations of rapid platelet recovery, durable responses, and an acceptable safety profile. The Noncommunicable Chronic Diseases-National Science and Technology Major Project, National Natural Science Foundation of China, CAMS Innovation Fund for Medical Sciences, National Key Research and Development Program of China, Tianjin Municipal Science and Technology Commission Grant, Joint Funds of the Natural Science Foundation of Tianjin, and China Higher Education Institution Industry-University-Research Innovation Fund.