Thalidomide promising for POEMS syndrome
medwireNews: Phase II/III trial results suggest that thalidomide could be a potential treatment option for patients with POEMS (polyneuropathy, organomegaly, endocrinopathy, M-protein and skin changes) syndrome who are not eligible for autologous transplantation.
The rare syndrome is characterised by overproduction of vascular endothelial growth factor (VEGF) and plasma cell dyscrasia, explain the study authors, making thalidomide, which suppresses both VEGF secretion and plasma cell proliferation, an attractive choice.
The Japanese POEMS Syndrome for Thalidomide (J-POST) trial enrolled 24 patients who were ineligible for autotransplantation from 12 hospitals. In the initial double-blind phase of the trial, 13 patients were randomly assigned to receive thalidomide 200 mg/day while 11 were given placebo, in both cases alongside dexamethasone 12 mg/m2 per day for the first 4 days of a 28-day cycle for up to six cycles.
Thalidomide treatment led to a significantly greater reduction in serum VEGF levels than placebo at 24 weeks, with an adjusted average reduction rate of 0.39 versus –0.02, giving an adjusted mean difference of 0.41.
The researchers also noted improvements in some secondary endpoints for the thalidomide versus placebo arms. For example, thalidomide-treated participants had improved motor function at 24 weeks, with greater changes in the sum muscle test scores – which included manual muscle testing, grip strength and overall neuropathy limitation scale – relative to placebo (adjusted mean between-group difference 3.01).
The incidence of adverse events was comparable between groups, with the exception of mild sinus bradycardia, which occurred in 54% of patients in the thalidomide group but in none of those given placebo.
A total of five study participants – three in the thalidomide and two in the placebo arm – experienced a serious adverse event, but there was no mortality in this part of the trial.
Twenty-two of the recruited patients continued into the second part of the study, in which all participants received open-label thalidomide 200 mg/day for 48 weeks.
Lead author Satoshi Kuwabara, from Chiba University, and colleagues report that an additional four patients developed sinus bradycardia, and there were five cases each of constipation and mild sensory neuropathy. Two patients, both of whom had received placebo initially, died during this 48-week period as a result of disease progression.
They summarise that their results show that thalidomide is a “new treatment option” for this patient population for whom no consensus therapy currently exists.
In a comment accompanying the report published in The Lancet Neurology, Arnaud Jaccard and Laurent Magy, both from University Hospital of Limoges in France, congratulate the study authors for conducting the first randomised trial in patients with POEMS syndrome.
But given the small number of participants and the “far from impressive” effects of thalidomide relative to placebo on the neurological clinical and laboratory endpoints, they do not believe that the study defines a new standard of care for these patients.
However, the trial “confirms the interest of using immunomodulatory drugs for POEMS syndrome and clearly shows that prospective and even randomised trials are feasible in this rare disease”, the commentators conclude.
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