Fluge et al. (2026)
- Authors: Øystein Fluge, Ingrid Gurvin Rekeland, Kari Sørland, Olav Mella
- Institutes: Haukeland University Hospital, Bergen, Norway, Oslo University Hospital, Oslo, Norway
- Publisher: ME/CFS Research Foundation Conference 2026
- Link: DOI
Summary
This trial is one of the most important current placebo-controlled tests of plasma cell depletion as a potential treatment for ME/CFS. By focusing on a specific immunological subset (patients with higher baseline NK cells), the study aims to move away from broad treatments toward more stratified medicine. If successful, it would strengthen the case that long-lived autoantibodies contribute to symptoms in at least a subgroup of patients and could help define future biomarker-guided trials. The update is encouraging, but it comes from conference and social-media reporting while the full blinded dataset is still pending.
What was researched?
The ResetME trial is a Phase II randomized controlled trial investigating whether depleting antibody-producing plasma cells with the drug daratumumab 💊 leads to clinical improvement in ME/CFS. It builds on previous pilot data suggesting a specific subset of patients may experience significant recovery through this mechanism.
Why was it researched?
Previous research by the Bergen group suggested that some ME/CFS symptoms may be driven by functional autoantibodies produced by long-lived plasma cells. Since these cells are not reliably removed by standard B-cell treatments like rituximab, researchers moved to daratumumab to target the CD38 marker on plasma cells themselves.
How was it researched?
The study is a double-blind, placebo-controlled trial involving a target of 66 participants with moderate to severe ME/CFS (CCC criteria). Participants are randomized to receive either active daratumumab or a placebo via subcutaneous injection. A specific inclusion threshold for Natural Killer (NK) cells (>125 x 10^6/L) is used to select patients most likely to respond based on pilot findings.
What has been found?
At the 2026 conference update, 38 of the 66 patients had reportedly been enrolled, with 17 completing the initial 8-week follow-up. Prior pilot results suggested that a subset of participants experienced marked clinical improvement. The new conference report also described larger changes in the autoantibody profile (autoreactome) among responders, raising the possibility that daratumumab may alter long-lived autoreactivity in some patients.
Discussion
The trial is still ongoing and remains blinded, meaning official efficacy results for the full cohort are pending. Safety monitoring has noted one serious adverse event involving a brief hospitalization for symptom worsening, highlighting the need for careful clinical supervision during treatment. The use of a strict NK-cell biomarker for inclusion is a novel approach to address patient heterogeneity.
Conclusion & Future Work
The ResetME trial appears to be progressing through recruitment and early follow-up. While results are not yet final, the study provides a serious framework for testing whether plasma cell depletion can help a defined ME/CFS subgroup. Further updates are expected as the full cohort completes longer follow-up.