A Novel Approach to Treating Refractory Immune Thrombocytopenia

CM313 is a novel (non–FDA-approved) anti-CD38 monoclonal antibody designed to deplete plasma cells and other immune cells involved in the pathogenesis of immune thrombocytopenic purpura (ITP). This phase 1/2, open-label study from China evaluated safety and efficacy of intravenous CM313 (16 mg/kg weekly for 8 weeks) in 22 adult patients with primary ITP refractory to at least one prior therapy (platelet count, <30 x 10⁹/L). Concomitant ITP therapies, including steroids, were allowed, and posttreatment follow-up lasted 16 weeks.

CM313 was generally well-tolerated, with infusion-related reactions being the most common adverse events, occurring in seven patients. Regarding efficacy, 21 patients achieved the desired platelet response (≥2 consecutive measurements of ≥50 x 10⁹/L during treatment), and 14 patients maintained a durable response for at least 8 weeks. The median time to response was 1 week, and median duration of response was 23 weeks. Additionally, 14 patients reported reductions in bleeding symptoms. Antidrug antibodies were clinically insignificant.

In translational studies, responders had reductions in antiplatelet autoantibodies and normalization of T cell subsets. Immune response modulation was evidenced by decreased CD38+ plasma cells, increased T-regulatory cells, suppressed lymphocyte proliferative function, and reduced IgG levels.