Immunomodulatory Drugs

Both immunomodulatory therapy and IST have been tried in patients with MDS. Thalidomide is an immunomodulatory agent with numerous cytokine-altering and antiangiogenic effects.28 29 On the basis of its significant clinical activity in multiple myeloma,30 thalidomide has been given to MDS patients in attempts to favorably modify the bone marrow cytokine milieu and possibly impair angiogenesis. Thalidomide appears to have mostly erythropoietic activity in MDS, but it is not well tolerated. In one phase II thalidomide study, 51 of 83 patients were able to complete 12 weeks of thalidomide therapy, and 15 had an erythroid response31 using the International Working Group response criteria. While 11 patients (13%) had a major erythroid response (a hemoglobin rise of >2 gm/dL or loss of transfusion dependence), 32 patients (38%) were removed from the study or they withdrew their consent because of excessive toxi-city, progression of disease, or other medical problems. Similar results have been obtained in other trials of thalidomide in MDS, as summarized in Table 40.2. Although anemia may be significantly improved, myelosuppression is often seen, and it is difficult to predict who will respond to thalidomide. While a North American phase III trial comparing thalidomide to supportive care has been completed, its outcome has not yet been reported.

Another "immunomodulatory" agent, CC-5013 (lenalidomide), appears to have greater erythropoietic activity than does thalidomide in PRBC transfusion-dependent MDS patients. A phase I/II clinical trial of lenalidomide in MDS patients was presented at the 2003 American Society of Hematology Annual Meeting. The 33 enrolled patients had primarily low-risk MDS by IPSS score (88% were in the Low/Int-1 group) and all had significant anemia (Hgb level <9g/dL or transfusion dependent). The overall erythroid response rate was 64%, with a 58% major erythroid response rate.32 Many patients had received, but had not responded to, thalidomide or rHuEPO therapy. The median increase in hemoglobin level was 4.4 g/dL in responding patients, and the time to treatment failure was 19-71 +

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