NCCN Clinical Practice Guidelines in Multiple Myeloma identify thalidomide as an appropriate salvage therapy for relapsed or refractory disease. (NCCN, 2004) The activity of thalidomide as single agent therapy in patients with relapsed and refractory myeloma has been demonstrated in numerous studies, the first of which was published by Singhal et al in 1999 in the New England Journal of Medicine. Some of the earlier studies reported overall response rates (typically defined as ≥25% reduction in M protein) from 24% to 78%.

Responses to treatment are now more often reported based on the percent reduction in myeloma protein. A summary of recent trials of thalidomide as single-agent therapy in relapsed and refractory patients is shown below. The data from these studies can be summarized as follows:

• M-protein reductions of ≥50% were reported in up to 48% of patients.
• Small numbers of patients (1-8%) achieved a complete response.
• Evidence of response was noted as early as 4 weeks. Reported median times to response were about 2 to 3 months, with individual times to response of up to 9 months.
• There is a suggestion of improved response with continued therapy.
• When reported, median duration of response ranged from 8 to 11.5 months, while individual responses were maintained from 2 to 30 months.
• Thalidomide doses ranged from 50 mg/day or less to 800 mg/day.

Although no controlled trials have examined survival, retrospective analyses indicate that higher cumulative doses of thalidomide in the first 3 months predicted superior overall and event-free survival than lower cumulative doses. In the largest trial to date (Barlogie et al, Blood. 2002;100(11):210a. Abstract 789), 4-year event-free and overall survival were 9% and 25%, respectively.

While the results of this and other clinical trials conducted between 2001 and 2003 (see table below) show the efficacy of thalidomide as a single-agent therapy for patients with relapsed and refractory multiple myeloma, due to toxicity, the majority of trials now focus on thalidomide in combination with other anticancer agents.