Intravenous Cyclophosphamide in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. An Open-Label Phase II Study

• Published in: Frontiers in medicine Vol. 7; p. 162
• Main Authors: Rekeland, Ingrid G, Fosså, Alexander, Lande, Asgeir, Ktoridou-Valen, Irini, Sørland, Kari, Holsen, Mari, Tronstad, Karl J, Risa, Kristin, Alme, Kine, Viken, Marte K, Lie, Benedicte A, Dahl, Olav, Mella, Olav, Fluge, Øystein
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 29.04.2020
• Subjects: CFS; chronic fatigue syndrome; clinical trial; cyclophosphamide; Medicine; myalgic encephalomyelitis; clinical trial; CFS; medical treatment; ME; chronic fatigue syndrome; cyclophosphamide; myalgic encephalomyelitis; HLA
• ISSN: 2296-858X; 2296-858X
• DOI: 10.3389/fmed.2020.00162

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a disease with high symptom burden, of unknown etiology, with no established treatment. We observed patients with long-standing ME/CFS who got cancer, and who reported improvement of ME/CFS symptoms after chemotherapy including cyclophosphamide, forming the basis for this prospective trial. This open-label phase II trial included 40 patients with ME/CFS diagnosed by Canadian criteria. Treatment consisted of six intravenous infusions of cyclophosphamide, 600-700 mg/m , given at four-week intervals with follow-up for 18 months, extended to 4 years. Response was defined by self-reported improvements in symptoms by Fatigue score, supported by Short Form 36 (SF-36) scores, physical activity measures and other instruments. Repeated measures of outcome variables were assessed by General linear models. Responses were correlated with specific Human Leukocyte Antigen (HLA) alleles. The overall response rate by Fatigue score was 55.0% (22 of 40 patients). Fatigue score and other outcome variables showed significant improvements compared to baseline. The SF-36 Physical Function score increased from mean 33.0 at baseline to 51.5 at 18 months (all patients), and from mean 35.0 to 69.5 among responders. Mean steps per 24 h increased from mean 3,199 at baseline to 4,347 at 18 months (all patients), and from 3,622 to 5,589 among responders. At extended follow-up to 4 years 68% (15 of 22 responders) were still in remission. Patients positive for HLA-DQB1 03:03 and/or HLA-C 07:04 ( = 12) had significantly higher response rate compared to patients negative for these alleles ( = 28), 83 vs. 43%, respectively. Nausea and constipation were common grade 1-2 adverse events. There were one suspected unexpected serious adverse reaction (aggravated POTS) and 11 serious adverse events in eight patients. Intravenous cyclophosphamide treatment was feasible for ME/CFS patients and associated with an acceptable toxicity profile. More than half of the patients responded and with prolonged follow-up, a considerable proportion of patients reported ongoing remission. Without a placebo group, clinical response data must be interpreted with caution. We nevertheless believe a future randomized trial is warranted. www.ClinicalTrials.gov, identifier: NCT02444091.