Randomized clinical trial of thalidomide, cyclosporine, and prednisone versus cyclosporine and prednisone as initial therapy for chronic graft-versus-host disease

Chronic graft-versus-host disease (CGVHD) is a major cause of morbidity fol lowing allogeneic bone marrow transplantation. Thalidomide is active in sal vage therapy for high-risk or resistant CGVHD. In a prospective randomized trial, we tested initial therapy with thalidomide. Patients with extensive CGVHD were randomized to receive either cyclosporine and alternate-day pred nisone (n = 27, no-thalidomide [no-thal] group) or cyclosporine, prednisone , and thalidomide (200-800 mg/day; n = 27, thal group). Although most patie nts responded, initial therapy with thalidomide did not improve control of CGVHD. Response rates were 83% versus 89% at 2 months (P = .7), 88% versus 84% at 6 months (P > .8) and 85% versus 73% at 1 year (P = .5) in the thal and no-thal groups, respectively. Multivariate analysis revealed related do nor transplant (odds ratio [OR] = 11.3; P = .03) and de novo or quiescent o nset of CGVHD (OR = 7.7; P = .04) to be significant predictors of good earl y response, whereas a platelet count of greater than or equal to 100,000/mu L was a significant predictor of good response (OR = 10.4; P = .04) at 1 ye ar. Survival for the thal and nothal groups was similar at 1 year (66% vers us 74%) and 2 years (66% versus 54%, P = .85). Multivariate analysis reveal ed progressive onset CGVHD (relative risk [RR] = 4.2; P = .01), unrelated d onor (RR = 5.7; P < .01), sex mismatch (RR = 7.9; P < .01), and platelet co unts of < 100,000/muL (RR = 3.8; P = .01) as significant predictors of poor er survival. These data suggest that despite a high response rate (79% resp onse and 53% complete response) and encouraging survival rates (70% at 1 ye ar and 60% at 2 years), thalidomide offers no clinical benefit when incorpo rated into initial therapy for CGVHD. The value of thalidomide as salvage t herapy requires further study.