Plasma cell targeting with the anti-CD38 antibody daratumumab in myalgic encephalomyelitis/chronic fatigue syndrome-a clinical pilot study.

Background: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) entails low quality of life for patients and massive societal costs. There is an urgent need for elucidation of disease mechanisms and for rational treatment. Our working hypothesis is that ME/CFS in a subgroup of patients is associated with functional autoantibodies emerging after an infection, and that plasma-cell depletion with transient reductions in serum immunoglobulins will have a beneficial effect on patients' symptoms. Objective: To evaluate feasibility and toxicity of plasma-cell targeting treatment using the subcutaneous anti-CD38 antibody daratumumab (Darzalex Methods: We performed a prospective, open-label pilot trial (EudraCT 2022-000281-18). Ten female patients were enrolled. Following 12 weeks run-in, six patients received four daratumumab injections. The next four patients received four, followed by three additional injections from week 14. Results: All planned treatments were administered, and there were no serious adverse events. Four patients had no significant clinical changes. Six patients experienced marked improvement. For all 10 patients, mean SF-36 Physical Function (SF-36 PF) increased from 25.9 to 55.0 at 8-9 months ( Conclusion: Subcutaneous daratumumab in 10 ME/CFS patients was well tolerated. In six patients, treatment was associated with clinical improvement and concurrent transient reduction of serum IgG levels, indicating important pathomechanistic roles for long-lived plasma cells and functional autoantibodies. No definite conclusions should be drawn before a randomized study has been performed. Clinical trial registration: https://euclinicaltrials.eu, Identifier: 2022-000281-18.