Thalidomide Plus Prednisone Promising for Myelofibrosis With Myeloid Metaplasia

December 13, 2002

Dec. 13, 2002 (Philadelphia) — An experimental regimen of low-dose thalidomide and the steroid prednisone was effective against anemia and thrombocytopenia in a three-month pilot study enrolling 21 patients who had myelofibrosis with myeloid metaplasia (MMM).

Ruben A. Mesa, MD, and his colleagues at the Mayo Clinic in Rochester, Minnesota, were able to palliate anemia in 62% and thrombocytopenia in 75% of the patients. Activity against splenomegaly was more limited; four patients had a >50% reduction in spleen size.

Dr. Mesa presented the results here at the American Society of Hematology meeting. He described the combination of the most effective regimen to date for treatment of anemia and thrombocytopenia associated with MMM.

The only effective cure for MMM is transplant, according to Dr. Mesa, and it cannot be used in most patients because of age and toxicity. No medical therapy has been shown to improve survival, he said.

The thalidomide-prednisone combination (THAL Pred) did not appear to have an impact on bone marrow angiogenesis. Although the investigators had hoped to target MMM, they saw value in relieving the accompanying conditions.

"Very little has previously been shown to improve thrombocytopenia," Dr. Mesa told Medscape. "The regimen did not change the marrow manifestations at all, so it is probably strictly palliative. But palliative is worth considering in symptomatic MMM patients with anemia and/or thrombocytopenia." The investigators had previously reported that oral thalidomide, started at 200 mg per day, improves anemia in 20% of MMM patients. Toxicities were seen in a majority of patients, however. Only 53% of patients in that prior study had been able to tolerate three months of thalidomide therapy.

In the new study, the thalidomide dose was lowered to 50 mg per day. Patients also received a tapering dose of prednisone, starting at 0.5 mg/kg per day for the first month. Patients who responded after the first three months of therapy were allowed to continue for an additional three months.

All but one patient (95%) were able to complete the thalidomide-prednisone regimen. The most common toxicities were constipation and leukocytosis, each at 38%, followed by mild neuropathy and mild sedation, each at 29%. Although patients also experienced toxicities associated with corticosteroid use — including hyperglycemia (24%), visual changes (19%), and anxiety (19%) — these were said to be mild and transient.

In addition, 19% of patients had thrombocytosis, but only one patient experienced thrombosis.

Ten of the patients who responded initially were able to complete an additional three-month regimen with thalidomide alone. About two-thirds continued to have a sustained response with respect to anemia and thrombocytopenia, and half for splenomegaly.

"We are pleased with the results, but really wish to see a regimen with even better activity before pursuing phase III testing," Dr. Mesa said. "We are going to be looking at trials combining THAL Pred and other active agents, as well as newer analogs of thalidomide such as revimid." Richard T. Silver, MD, medical director of the leukemia and myeloproliferative center at Weill-Cornell Medical Center in New York City, told Medscape that any regimen that improves MMM symptoms is important. In his experience, patients have not been able to tolerate high doses of thalidomide, he said, questioning whether prednisone was of more value in the combination.

The results suggest prednisone might be worth exploring by itself or with interferon in another trial, Dr. Silver said. "If the marrow doesn't change and the spleen doesn't change, why did the patients get better?" he asked. "Maybe the prednisone did more than the thalodimide."

ASH 44th Annual Meeting: Abstract 258. Presented Dec. 9, 2002.

Reviewed by Gary D. Vogin, MD



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