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

Observed Findings

• Six of 10 patients (60%) experienced marked clinical improvement with treatment, while four showed no significant changes.
• Mean SF-36 Physical Function scores increased from 25.9 to 55.0 across all 10 patients (p=0.002), and from 32.2 to 78.3 in responders.
• Mean daily step count increased from 3,359 at baseline to 5,862 at 8-9 months overall, and to 7,392 in responders; five responders achieved >10,000 steps/day for some weeks.
• Serum IgG levels decreased 54% in clinical responders versus 40% in non-responders.
• Low baseline natural killer (NK) cell count was significantly associated with lack of clinical response.

Inferred Conclusions

• Subcutaneous daratumumab is well-tolerated in ME/CFS patients with acceptable safety profile and no serious adverse events.
• In a subset of ME/CFS patients, plasma cell depletion with concurrent IgG reduction is associated with sustained improvement in physical function and symptom severity.
• Functional autoantibodies and long-lived plasma cells may play pathomechanistic roles in ME/CFS pathogenesis, at least in treatment-responsive patients.
• Baseline NK-cell count may be a useful biomarker for predicting treatment response and identifying eligible patient populations for future trials.

Remaining Questions