The activity of thalidomide monotherapy in relapsed or refractory disease is widely accepted but many haematologists have observed better response rates with combination therapies. This communication aims to give an overview on the efficacy of these alternatives.Methods: Our group has performed two systematic reviews (thalidomide monotherapy: Glasmacher et al., Brit. J. Haematol. , 2005; 129 suppl 1: 24; thalidomide and dexamethasone combination therapy: submitted to ASH 2005). Furthermore a search of trials combining thalidomide, cyclophosphamide and dexamethasone (with or without further drugs) was performed. Only trials that included patients with relapsed or refractory multiple myeloma could be evaluated. Response was defined as a reduction of the monoclonal component by more than 50% in the absence of any sign of disease progression. Proportions and 95% confidence intervals were reported (Confidence Interval Analysis, Version 2.1.1, Southampton, UK, 2000).Results: Thalidomide monotherapy was administered in doses between 50–600 mg/d (median doses). Thalidomide in combination with dexamethasone was given in doses of 100–400 mg/d (median doses), dexamethasone was given 40 mg/d d1–4 every 3–4 weeks in 7 of 8 trials. Thalidomide dosage and combination therapy of trials adding Cy to thalidomide and dexamethasone are shown in Table 1. The response rates of the three different thalidomide applications are demonstrated Table 2.Conclusion: This compilation of data from phase II trials cannot replace a randomized trial and may be biased. With this limitation it seems that thalidomide combined with dexamethasone (response rate 51%) is more effective than monotherapy (response rate 29%) as the 95% confidence intervals for the response rates do not overlap. Whether a combination of thalidomide, dexamethasone and cyclophosphamide is more effective than thalidomide and dexamethasone alone cannot be decided from the current data.Table 1:Studies with thalidomide and combination chemotherapyStudyInterventionNo. of pts.Response (95%CI)Moehler et al. 2003Cy 1600, Eto 160, T 400, Dex 16011955% (46–65)Kropff et al., 2003Cy 1800, T 400, Dex 2406070% (57–81)Dimopoulos et al. 2003Cy 1500, T 400, Dex 1604367% (51–81)Gracia-Sanz et al. 2004Cy 50 daily, T 800, Dex 1607157% (45–67)Glasmacher et al. 2005Cy 800, Ida 40, T 400, Dex 3203957% (41–73)Abb.: Cy, cyclophosphamide; Eto, etoposide; T, thalidomide; Dex, dexamethasone; Ida, idarubicin. Values are mg/m2 per course for Cy, Eto, Ida; mg per course for Dex, mg/d for T.Table 2:Response of different thalidomide combinationsInterventionNo. of trialsNo. of pts.Response (95%CI)T monotherapy42162929% (27–32)T + Dex828351% (45–57)T + Cy + Dex533260% (55–65)Abb.: see Table 1