Norwegian Researchers Report Promising Results from Daratumumab Pilot Study in ME/CFS Patients
Key Insights
A pilot study at Haukeland University Hospital (search) in Norway tested daratumumab, an anti-CD38 (search) antibody, in 10 female patients with moderate to severe ME/CFS (search), finding that six patients experienced clinical improvement with five showing sustained benefits lasting 12-24 months.
The treatment targeted plasma cells believed to produce autoantibodies that may contribute to ME/CFS (search) symptoms, resulting in a mean 48% reduction in serum IgG levels and significant improvements in physical function scores from 25.9 to 55.0.
Researchers observed a correlation between baseline NK cell numbers and treatment response, with patients having higher NK cell counts at baseline showing better clinical outcomes, suggesting this could serve as a potential biomarker for treatment selection.
Norwegian researchers have reported encouraging results from a pilot study testing daratumumab, an anti-CD38 (search) monoclonal antibody, in patients with moderate to severe Myalgic Encephalomyelitis (search)/Chronic Fatigue Syndrome (search) (ME/CFS (search)). The open-label study, conducted at Haukeland University Hospital (search) in Bergen, Norway, represents the first known investigation of plasma cell-targeting therapy in ME/CFS patients.
Study Design and Patient Population
The prospective, single-center trial enrolled 10 female patients with moderate to severe ME/CFS (search) according to Canadian consensus criteria. All participants had disease duration of at least 2 years, with a mean age of 38 years and average disease duration of 12 years. Nine of the 10 patients had a defined immunological trigger, typically an infection, preceding their ME/CFS onset.
The study employed a 3-month run-in period to capture natural symptom variation before intervention. The first six patients received four subcutaneous daratumumab injections (1800 mg each) at weeks 0, 2, 4, and 6. The subsequent four patients received the same initial four injections plus three additional maintenance treatments at weeks 14, 22, and 30.
Clinical Outcomes Show Significant Improvement
Six out of 10 patients experienced clinical improvement during follow-up, with a remarkably homogeneous pattern of response beginning 6-8 weeks after the first injection. Among these responders, five patients demonstrated pronounced and sustained symptom alleviation lasting 12-24 months.
The clinical improvements were substantial across multiple measures. Mean SF-36 Physical Function scores increased from 25.9 at baseline to 55.0 at 8-9 months post-treatment. For the six patients with clinical improvement, scores rose from 32.2 to 78.3. Correspondingly, DePaul Symptom Questionnaire scores decreased from 72.3 to 43.1 overall, and from 71.1 to 24.3 in the improvement group.
Physical activity levels, continuously monitored via Fitbit devices, showed parallel improvements. Mean daily steps increased from 3,359 at baseline to 5,862 overall, with the improvement group showing an increase from 3,363 to 7,393 steps per day. All five patients with sustained clinical benefit recorded single weeks with approximately 10,000 or more daily steps.
Plasma Cell Depletion and Immunological Effects
The treatment achieved its intended plasma cell depletion, with mean serum IgG levels declining by 48% from baseline. The reduction was more pronounced in patients who experienced clinical improvement (54%) compared to non-responders (40%). The lowest mean serum IgG level of 5.5 g/L occurred at 5 months post-treatment.
Analysis of IgG subclasses revealed particularly notable reductions in IgG4 levels, with an overall 60% decrease. Among patients with clinical improvement, IgG4 reduction reached 65%, compared to only 29% in non-responders. IgG4 has unique characteristics and is often associated with autoimmune diseases that respond to B-cell depletion therapies.
NK Cell Numbers Predict Treatment Response
A significant correlation emerged between baseline natural killer (NK) cell numbers and clinical response. Patients with higher baseline NK cell counts (mean 238, range 136-383) showed clinical improvement, while those with lower counts (mean 97, range 80-115) did not respond to treatment. The correlation between baseline NK cells and maximum increase in SF-36 Physical Function was statistically significant (Spearman's rho 0.77, p = 0.012).
As expected, NK cell numbers declined following daratumumab treatment due to CD38 (search) expression on these cells, but gradually recovered to normal ranges by 15-21 months post-treatment.
Safety Profile and Tolerability
The treatment demonstrated excellent safety and tolerability. All patients experienced mild erythema at injection sites, classified as grade 1 adverse events. No serious adverse events, injection-related reactions, or allergic reactions occurred. Two patients experienced transient vision blurring, likely related to the study medication.
Common infections during follow-up, including COVID-19 (search), followed uncomplicated courses with no hospitalizations required. One patient developed an uncomplicated varicella zoster infection treated with oral antivirals.
Mechanistic Rationale and Future Directions
The researchers hypothesize that ME/CFS (search) involves autoantibodies produced by long-lived plasma cells that persist after initial infections. These functional autoantibodies may affect G-protein coupled receptors and other targets, leading to autonomic dysfunction and the characteristic symptoms of ME/CFS.
The study's findings support this autoimmune hypothesis, particularly given the correlation between plasma cell depletion (measured by IgG reduction) and clinical improvement. The researchers note that five patients maintained stable remission despite gradually increasing serum IgG levels toward the end of follow-up, suggesting possible lasting changes in the autoantibody repertoire.
Randomized Controlled Trial Launched
Based on these promising pilot results, the research team launched a randomized, double-blind, placebo-controlled study in June 2025. The new trial will include patients with moderate to severe ME/CFS (search) according to Canadian consensus criteria, with at least 2 years of disease duration. Long COVID (search) patients meeting inclusion criteria may also qualify for participation.
The researchers emphasize that while the pilot data are encouraging, definitive conclusions await results from the controlled trial. The study represents a significant step forward in ME/CFS (search) research, offering the first evidence that plasma cell-targeting therapy may benefit a subset of patients with this debilitating condition.