Imaging CD8+ T Cells in Patients With Inclusion Body Myositis (IBM) Treated With Ulviprubart
Michael Farwell1, Robert D. Henderson2, Merrilee Needham3, Dulce Soler-Ferran4, H. Jeffrey Wilkins4
1Division of Nuclear Medicine Imaging and Therapy, Hospital of the University of Pennsylvania, Philadelphia, PA, USA, 2Department of Neurology, Royal Brisbane & Women's Hospital, Brisbane, Queensland, Australia; University of Queensland Centre for Clinical Research, University of Queensland, Brisbane, Queensland, Australia, 3Perron Institute, QEII Medical Centre, Nedlands, Western Australia, Australia; University of Notre Dame, Perth, Western Australia, Australia; Fiona Stanley Hospital, Perth, Western Australia, Australia; Murdoch University, Perth, Western Australia, Australia, 4Abcuro, Inc., Newton, MA, USA
Background:
IBM is a rare, progressive disease characterized by invasion of healthy muscle by highly differentiated cytotoxic CD8+ T cells and associated with loss of grip strength, difficulty walking, and/or dysphagia. Ulviprubart is a monoclonal antibody that selectively depletes cytotoxic CD8+ KLRG1+ T cells by targeting the cell-surface marker KLRG1, which is found on the majority of IBM-muscle T cells and may have activity in patients with IBM. Here, an investigational positron emission tomography (PET) tracer was used for noninvasive imaging of skeletal muscle CD8+ T cells in patients with IBM following ulviprubart administration.
Design/Methods:
This was a substudy of an open-label phase 1 trial (NCT04659031). Patients with IBM received 1.0 mCi of the CD8+ T-cell−specific PET tracer [
89Zr]Zr-Df-crefmirlimab and underwent whole-body PET/CT imaging 24 hours later. Ulviprubart (2 mg/kg) was administered subcutaneously after the initial scan and at week 8. Pharmacodynamic activity in muscle (ie, tracer uptake) and blood was assessed at baseline and week 12.
Results:
Eight patients enrolled (75% male; mean age: 66.5 years); 2 patients with severe disease and minimal baseline tracer uptake were excluded. Five of 6 patients demonstrated reductions in tracer uptake (ie, CD8+ T-cell depletion) in ≥1 muscle group with ulviprubart. Mean percentage reductions were observed in the anterior calf (right, −23%; left, −19%), posterior calf (−14%; −15%), thigh (−14%; −15%), buttock (−13%; −16%), shoulder (−3%; −9%), and forearm (−6%; −4%). Five of 6 patients showed sustained depletion of CD8+ KLRG1+ cells in blood (maximum depletion, range: 90–100%). No serious adverse events or discontinuations due to adverse events were reported.
Conclusions:
In this study, 2 doses of ulviprubart treatment reduced CD8+ T cells in muscle, and ulviprubart was safe and well tolerated. These results suggest that ulviprubart has pharmacodynamic effects in skeletal muscle.
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