Issue: 2010 > July/August > review

Thalidomide and lenalidomide in primary myelofibrosis

N. Holle, T. de Witte, C. Mandigers, N. Schaap, R. Raymakers


Primary myelofibrosis is a clonal haematopoietic stem cell disease, characterised by marrow stromal fibrosis, extramedullary haematopoiesis, splenomegaly, hepatomegaly and progressive cytopenia. Therapeutic
options once cytopenia has developed are limited to
supportive care, such as erythrocyte transfusions and growth factors. The aetiology has become more clear, especially since JAK-2 mutations were found, resulting in increased production of cytokines. The immune-modulating drug thalidomide and its derivative lenalidomide have shown to be effective in reducing cytopenia, most probably by inhibiting the cytokine responses. In some patients the bone marrow fibrosis
disappears. We describe the experience with these drugs
in a cohort of 14 patients for thalidomide and seven for
lenalidomide (in six patients lenalidomide was given after thalidomide and one patient received lenalidomide
upfront). Thalidomide gave clinical improvement in 6/14 patients, but its use was limited mainly due to toxicity, especially the development of neuropathy. The drug could be given for a median period of 15.5 months in responding patients. Lenalidomide was effective in 4/7 of the patients, in some patients with no response on thalidomide. Due to the more favourable toxicity profile, the median duration of therapy was 19 months, with 3/4 patients on therapy longer than 19 months. These data are discussed in view of the clinical studies published. We conclude that lenalidomide is preferred in myelofibrosis, given a higher response rate and more
favourable toxicity profile. If no response the addition of
prednisone can be considered. In some patients it can
normalise haemoglobin and make them transfusion