Plonmarlimab, a GM-CSF-neutralizing antibody, for macrophage activation syndrome.

Authors

Jingshi Wang, Ran Wang, Qian Wang, Lin Wu, Wenfeng Tan, Jialin Teng, Ke Xu, Dongfei Yin, Yuan Meng, Xi Chen, Qiong Fu, Zhao Wang

Published in

Journal of hematology & oncology. Volume 19. Issue 1. Oct 28, 2026. Epub Oct 28, 2026.

Abstract

Macrophage activation syndrome (MAS) is a subtype of secondary hemophagocytic lymphohistiocytosis (sHLH) and a rare, life-threatening complication of uncontrolled rheumatic diseases, characterized by systemic inflammation driven by aberrant activation of macrophages. We aimed to assess the efficacy and safety of plonmarlimab, a high-affinity neutralizing monoclonal antibody targeting granulocyte-macrophage colony-stimulating factor (GM-CSF), for the treatment of MAS. In this phase 2, multicenter, open-label, single-arm clinical trial (NCT07034209 and CTR20230579), 18 patients with MAS secondary to systemic autoimmune rheumatic disease who were refractory to or had relapsed after high-dose glucocorticoid therapy were enrolled. Patients received plonmarlimab once weekly for 8 weeks at 6 mg/kg as the starting in the accelerated titration stage, and then at 10 mg/kg for the first two doses followed by dose adjustments at the investigator's discretion. The primary endpoint, overall response rate at week 8, was 83.3% (15/18) among all treated patients. The median time to response was 2.1 weeks (95% confidence interval [CI], 1.0-3.1), and the median time to remission of MAS symptoms was 1.1 weeks (95% CI, 1.0-2.3). The least-squares mean percentage reduction in glucocorticoid dose from baseline to week 8 was 79.3% (95% CI, 76.3-82.3), and 83.3% of patients (15/18) achieved a ≥ 50% reduction. No grade ≥ 3 infections were observed. Biomarker analysis showed rapid reductions in ferritin and interleukin (IL)-18 levels. Plonmarlimab showed promising clinical activity and was generally well tolerated in patients with MAS, and IL-18 may serve as a potential pharmacodynamic marker for GM-CSF antibody therapy.

PMID:
42958582
Bibliographic data and abstract were imported from PubMed on 30 Oct 2026.

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