Activity of Thalidomide in Waldenström’s Macroglobulinemia

Thalidomide (Thalomid) is a potent teratogen and sedative that inhibits angiogenesis. Based on the activity of this agent in patients with multiple myeloma, we initiated a phase II study in Waldenstrom’s macroglobulinemia.

Oral thalidomide was administered on a dose-escalating schedule of 200 mg daily ´ 14 days, with a dose escalation of 200 mg every 2 weeks to a maximum dose of 600 mg. Between July and November 1999, eight patients were included. The median age was 72 years (range: 63–84 years), hemoglobin was < 10.0 g/dL in four patients, serum monoclonal IgM was > 3.0 g/dL in seven patients, and lymphadenopathy or splenomegaly was present in six patients. Three patients were previously untreated, three were primary refractory and two were treated during refractory relapse.

Among the seven patients evaluable for response so far, three have achieved at least a 50% reduction of serum monoclonal protein, in one patient the serum monoclonal protein was stable, and in three patients there was disease progression. At least a 25% protein reduction was noted in the three eventual responders within 4 weeks of thalidomide therapy. A significant reduction of organomegaly and splenomegaly occurred in responding patients. Toxicities included transient somnolence in all patients, moderate fatigue in three patients, and severe constipation in four patients; mild myelosuppression and tremor were noted in one patient each.

CONCLUSION: While patient accrual is ongoing, it appears that thalidomide has a biologic effect in Waldenstrom’s macroglobulinemia.

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