Cancer drug cyclophosphamide shows ME/CFS is treatable
Dr Øystein Fluge & Dr Ingrid Rekeland
Norwegian scientists have been testing 2 cancer drugs on ME patients for 6 years, following a surprise recovery from ME when being treated for cancer. Patients with ME/CFS enrolled in the two clinical intervention trials RituxME and CycloME.
They have found that patients treated with cyclophosphamide reported greater and more lasting improvements than those treated with rituximab or placebo.
However these drugs are toxic and can cause severe side effects. They do not recommend cyclo as a treatment, but “these data should encourage efforts to better understand the disease mechanisms and to search for targeted and less toxic immune modulatory treatment for this patient group.”
They also acknowledge that “it is difficult to assess whether symptom improvement in a clinical trial can be attributed to the intervention or to other factors. During the trials, placebo mechanisms may contribute, and participants can also be affected by being taken care of in a clinical study (“trial effect”). A modest, but evident rate of recovery in the placebo group indicates a potential for spontaneous improvement, suggesting that ME/CFS is in principle a reversible disease.
Six-year follow-up of participants in two clinical trials of rituximab or cyclophosphamide in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome by Ingrid G. Rekeland, Kari Sørland, Lisbeth Lykke Neteland, Alexander Fosså, Kine Alme, Kristin Risa, Olav Dahl, Karl J. Tronstad, Olav Mella, Øystein Fluge in PLoS ONE 19(7): e0307484. 2024[doi.org/10.1371/journal.pone.0307484]
Research abstract
Objectives
In this six-year follow-up study, we used patient-reported outcome measures (PROMs) to compare values at baseline, at 18 months, and at six-year follow up from the CycloME and the RituxME trials.
Methods
Based on the hypothesis that ME/CFS in a subgroup of patients is a variant of an autoimmune disease, we performed two clinical trials between 2014 and 2017. The RituxME trial was a randomized, double-blind and placebo-controlled phase III trial of 151 patients, assessing the B-cell depleting antibody rituximab.
The CycloME trial was an open-label phase II trial of 40 patients using intravenous cyclophosphamide. Here we report six-year follow-up from both trials, using the Short Form 36 Physical Function (SF-36 PF) and DePaul short form (DSQ-SF) questionnaires.
Result
Of the patients available after six years, 75.7% of RituxME and 94.4% of CycloME patients participated. In the RituxME rituximab group, the mean SF-36 PF scores were 32.9 at baseline, 42.4 at 18 months and 45.5 at six years. In the placebo group, the mean SF-36 PF scores were 32.3 at baseline, 45.5 at 18 months and 43.1 at six years. In the CycloME trial, mean SF-36 PF increased from 35.4 at baseline to 54.4 at 18 months, and 56.7 at six years.
At six-year follow-up, 44.1% of cyclophosphamide-, 27.6% of rituximab- and 20.4% of placebo-treated patients had an SF-36 PF ≥ 70, and further, 17.6%, 8.6% and 7.4% of the corresponding patient groups had an SF-36 PF ≥ 90, which is within normal range. In terms of worsening at six years, 5.9% of cyclophosphamide-treated, 10.3% of rituximab-, and 14.8% of placebo-treated patients had a drop in SF-36 PF of 20 points or more from baseline. There were no serious unexpected adverse reactions.
Conclusions
After six years, 44.1% of the cyclophosphamide group scored an SF-36 PF of at least 70, and 17.6% of at least 90, suggesting that cyclophosphamide in a subgroup may modulate the disease course in a beneficial way. However, cyclophosphamide carries toxicity concerns and should not be used for ME/CFS patients outside clinical trials. Rather, these data should encourage efforts to better understand the disease mechanisms and to search for targeted and less toxic immune modulatory treatment for this patient group.
