A Combination of Low Dose Thalidomide with Prednisone in Myelofibrosis with Myeloid Metaplasia

Reviewer: Tracy d'Entremont, MD
Last Modified: December 9, 2002

Presenter: Ruben A. Mesa
Presenter's Affiliation: Mayo Clinic; Rochester, MN
Type of Session: Scientific


  • Myelofibriosis with Myeloid Metaplasia (MMM) is a clonal myeloproliferative disorder with varied prognosis and severity.
  • A curative therapy is lacking for this disease, although peripheral stem cell transplant may be an option for a certain subset of patients.
  • Medical therapies to date have failed to demonstrate a clear survival advantage and have only resulted in palliation.
  • Thalidomide, an anti-angiogenesis agent, is of interest in MMM because MMM is marked by a significant degree of angiogenesis in the bone marrow.
  • Thalidomide at a dose of 200mg/day demonstrates improvement in anemia in some patients with MMM but over half of the patients were unable to tolerate three months of therapy due to toxicity.
  • In an effort to improve drug tolerance as well as response rate, this study was designed using a low dose thalidomide in combination with prednisone for patients with MMM.

Materials and Methods

  • This phase II study enrolled patients with MMM who had symptomatic splenomegaly or anemia with hgb < 10g/dl.
  • Treatment for the first 1 month consisted of thalidomide at 50mg/day and prednisone at 0.5mg/kg/day; the thalidomide dose was continued for 3 months but the prednisone was tapered in the following schedule; 0.25mg/kg/day for month 2; and 0.125mg/kg/day for month 3.
  • After three months of combination therapy, patients were evaluated for response, those responding were continued on thalidomide alone for an additional three months.


  • A total of 21 patients with MMM were enrolled
  • 20 patients (95%) were able to complete the first 3 months of scheduled therapy.
  • An objective clinical response was demonstrated in 13/21 (62%)
    all demonstrated improvement in anemia
    6/8 (75%) had improved plt counts
    4/21 (19%)had >50% dec in spleen size
  • Toxicities included: constipation (38%), leukocytosis (38%), mild neuropathy (29%), and mild sedation (29%).
  • 10/13 initial responders completed the thalidomide alone arm and clinical responses for the following parameters were sustained:
    anemia-- 62% of patients
    thrombocytopenia-- 66% of patients
    splenomegaly-- 50% of patients
  • Responses were not associated with changes in bone marrow fibrosis, cellularity, osteosclerosis, or angiogenesis.
  • Univariate analysis identified the following characteristics as predictive of response to therapy: lower pre-treatment peripheral blood CD34+ cells, decreased circulating blasts, increased baseline degree of angiogenesis, and smaller spleen size.
  • In multivariate analysis, none of these factors were significant

Author's Conclusions

  • A combination of low-dose thalidomide and prednisone is well tolerated and may be the most effective drug regimen, to date for the treatment of anemia and thrombocytopenia in patients with MMM.

Clinical/Scientific Implications

    This small phase II study of low-dose thalidomide in MMM is interesting. The mechanism of action of thalidomide at this dose is not clear as markers for angiogenesis did not seem to correlate with response rate. There was minimal response in terms of spleen size in these patients and unfortunately, most patients who need treatment for MMM have markedly enlarged and symptomatic splenomegaly. The authors concede that for those patients additional therapy will also be needed to control the splenomegaly. Although this is a potential new therapeutic option in MMM, clearly new therapies that will effect the clonal process in the marrow are necessary to make greater in-roads into improving survival for this disease.

Oncolink's ASH Coverage made possible by an unrestricted Educational Grant from Ortho Biotech.