Drugs used to treat thrombocytopenia in patients with myelodysplastic syndrome (MDS) do not cause disease progression or leukaemic transformation as previously feared, new findings suggest.
A trial of the thrombomimetic drug romiplostim in patients with lower risk MDS was terminated early in 2011 after transient increases were seen in blast cell counts and suggestions of a higher risk for progression to acute myeloid leukemia in patients treated with the drug.
However longer term follow up of the 250 patients in the trial has not found any increase in leukaemic transformation with romiplostin compared to placebo, according to findings published in Lancet Haematology.
Follow up of the phase 2 study of romiplostin as a treatment for thrombocytopenia – which included patients with MDS from the Royal Melbourne Hospital – found no difference in rates of acute myeloid leukaemia and death between active and placebo arms of the study.
After a median follow up of 27 months there were 20 cases (12%) of leukaemic transformation among the 167 patients treated with romiplostin for one year, compared to nine of 83 patients (11%) with MDS in the placebo group. Mortality rates were 56% versus 54%) for the two groups with follow up of up to five years.
The 25 patients in whom transient blast cell counts had been reported showed decrased counts on follow up data, the researchers noted.
“Thus over the course of this trial we found that romiplostin reduced platelet transfusions and bleeding with no long term increase in AML incidence or impact on survival,” concluded the authors, who included Professor Jeffrey Szer of the Department of Clinical Haematology at the University of Melbourne.
The researchers said there had previously been great enthusiasm for romiplostin as a treatment for thrombocytopaemia, which occurs in up to 80% of patients with MDS and is associated with poor prognosis and increased risk of bleeding.
The new findings would help inform haematologists treating patients with MDS where therapies for thrombocytopaemia were scarce, they said.
However the acknowledged that the findings came from an incomplete trial and only related to about one year of romiplostin treatment.
An accompanying commentary described the findings as good news for patients with MDS, but also cautioned that little was known about the effects of longer term treatment with romiplostin – and its counterpart eltrombopag – on disease progression.
“Caution is still required and additional research is warranted, but this knowledge justifies renewing the joint regulatory, pharmaceutical and medical efforts by returning to research and development options,” it concluded.