Bortezomib and Thalidomide, a Steroid Free Regimen in Newly Diagnosed Patients with Multiple Myeloma.

Abstract 2867

Poster Board II-843

Corticosteroids have historically been the backbone of most myeloma targeted therapies. However, they are often the major cause of toxicities, especially in elderly patients. In recent years, novel agents such as bortezomib and thalidomide have demonstrated significant anti-myeloma activity with increased overall response rates. We thus designed a study combining these two agents in a steroid-free regimen. Bortezomib (B) and thalidomide (T) were examined as first line treatment in 27 patients with symptomatic multiple myeloma between September 2004 and September 2006. Patients received B 1.3 mg/m² on days 1, 4, 8 and 11 every 21 days and T 150 mg daily for a maximum of 8 cycles. The overall response rate was 81.5%, with a near CR or greater of 25.8% and a CR (immunofixation negative) of 11%. A major response identified by greater than 90% reduction in the paraprotein was seen in 33% of the patients. Responses were rapid: median time to first response was 36.5 days (range, 14-101 days) and median time to best response was 61 days (range, 16-171 days). The most common grade 3 toxicities were peripheral neuropathy (22%), pneumonia (15%) and fatigue (7%). The only grade 3 hematologic toxicity was anemia (7%). No grade 4 toxicities were seen. 3 patients had mild peripheral neuropathy (PN) at baseline. PN was the most common reason for dose reduction with an average B dose of 1.1mg/m² and T of 110mg daily. The major cause of discontinuation of treatment was PN. The PN completely resolved in 80% of the patients upon completion of therapy. No venous thromboembolic events (VTE) were observed even in the absence of prophylactic anticoagulation. It should be noted that upon completion of the study all patients received either B or T maintenance and no patients proceeded onto stem cell transplant immediately. The median progression free survival (PFS) was 16.8 months (95% CI 8.7-21.6 months). Median overall survival has not yet been reached at a median follow up of 39 months. The 3 year overall survival is 74%. This study demonstrates: 1) the excellent efficacy of a steroid-free regimen; 2) good PFS in the absence of stem cell transplantation; and 3) that most treatment-related PN resolves.