Thalidomide and CC-5013 in multiple myeloma: the University of Arkansas experience.

Based on the activity of single-agent thalidomide in relapsed/refractory multiple myeloma in a landmark phase II study of 169 patients conducted at the University of Arkansas for Medical Sciences (UAMS), UAMS initiated several trials of thalidomide and the more potent thalidomide analog CC-5013. In an ongoing trial evaluating thalidomide plus the proteasome inhibitor bortezomib and dexamethasone in patients with relapsed/refractory disease following stem cell transplantation, approximately 50% of patients have experienced a paraprotein reduction of 50% or greater. In patients without cytogenetic abnormalities, the estimated 12-month event-free and overall survival rates are 69% and 100%, respectively. In a second ongoing trial building on the UAMS Total Therapy I regimen, newly diagnosed patients are randomized to thalidomide or no thalidomide pretransplantation followed by consolidation therapy with dexamethasone and multiagent chemotherapy post-transplantation (Total Therapy II). Although the Total Therapy II regimen appears to be superior to the original Total Therapy I regimen, assessment of the effect of thalidomide on Total Therapy II is pending accrual completion. Lastly, based on the increased potency and reduced toxicity profile of CC-5013 compared with thalidomide, a study of CC-5013 in patients with relapsed/refractory disease following transplantation was initiated. Patients are randomized to CC-5013 25 mg daily for 20 days versus CC-5013 50 mg every other day for 10 days. Preliminary results indicate the superiority of the 25-mg arm, with 40% of patients randomized to that arm experiencing a paraprotein reduction of 50% or greater. These preliminary results corroborate the role for thalidomide and CC-5013 in relapsed/refractory and newly diagnosed multiple myeloma based on the UAMS phase II study as well as several other studies of these agents outside of UAMS.

RCT Entities:   Population Interventions Outcomes