Intravenous Cyclophosphamide in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. An Open-Label Phase II Study.
Rekeland, Ingrid G, Fosså, Alexander, Lande, Asgeir et al. · Frontiers in medicine · 2020 · DOI
Quick Summary
Researchers tested whether cyclophosphamide, a chemotherapy drug, could help people with ME/CFS based on observations that some patients improved after cancer treatment. Forty patients received six infusions of this drug over six months, with check-ins lasting up to four years. More than half the patients reported meaningful improvements in fatigue and physical activity, with many staying better even years later.
Why It Matters
This study provides preliminary evidence that cyclophosphamide may induce sustained symptom remission in ME/CFS, addressing a disease with no established treatments. The identification of HLA alleles associated with treatment response offers potential biomarkers for patient stratification in future trials and suggests an immunological pathogenic mechanism.
Observed Findings
55% of 40 patients showed response by Fatigue score, with 68% of responders still in remission at 4-year follow-up.
SF-36 Physical Function increased from 33.0 to 51.5 in all patients and from 35.0 to 69.5 among responders at 18 months.
Mean daily steps increased from 3,199 to 4,347 across all patients and from 3,622 to 5,589 among responders at 18 months.
Patients with HLA-DQB1*03:03 and/or HLA-C*07:04 alleles had significantly higher response rates (83% vs 43%).
Most adverse events were grade 1-2 (nausea, constipation); one possible serious adverse reaction (aggravated POTS) and 11 serious adverse events occurred in eight patients.
Inferred Conclusions
Cyclophosphamide is feasible to administer to ME/CFS patients with an acceptable toxicity profile and may induce durable symptom improvement in a subset of patients.
HLA alleles DQB1*03:03 and/or C*07:04 are associated with treatment response and may identify patients most likely to benefit.
The prolonged remission observed in responders (68% at 4 years) suggests potential disease modification rather than temporary symptom suppression.
A randomized, placebo-controlled trial is warranted despite the open-label design limitations.
Remaining Questions
What This Study Does Not Prove
Without a placebo control, this study cannot definitively separate drug effect from natural history, regression to the mean, or expectations associated with intensive medical intervention. The open-label design introduces bias, and the small sample size limits generalizability. Long-term spontaneous remission rates in untreated ME/CFS are unknown, making it difficult to attribute observed improvements solely to cyclophosphamide.
Tags
Symptom:Orthostatic IntoleranceFatigue
Biomarker:Autoantibodies
Method Flag:No ControlsSmall SampleExploratory Only