Phase III trial of Velcade shows fourfold increase in remission rates

The phase III clinical trials investigated the efficacy of Velcade in the pre- and post- autologous stem-cell transplantation (ASCT) treatment of previously untreated multiple myeloma patients. A fourfold increase in remission rates was observed in patients administered Velcade combined with the most commonly used regimen for front-line multiple myeloma treatment in the US. Results from the trial were presented at the 49th Annual Conference of the ASH (American Society of Hematology) held in Atlanta, Georgia, December 8-11th 2007.

Multiple Myeloma (MM) is a progressive haematological disease that accounts for approximately 10% of hematologic malignancies.¹ MM is associated with a range of pathological disease manifestations, including osteolytic lesions, anemia, organ damage and immunosuppression due to loss of normal hematopoietic stem cell function.^2,3 About 74000 new cases of MM are diagnosed each year worldwide.⁴

Treatments for multiple myeloma have developed significantly over the last decade, with the introduction of drugs such as thalidomide, bortezomib and lenalidomide used as induction therapies for patients eligible for autologous stem-cell transplantation (ASCT).¹ Velcade (generic name: bortezomib) is an inhibitor of the 26S proteasome and NF-kappaB it is used in the treatment of a number of solid and haematological tumours.⁵

This multi-centre, randomised, phase III clinical trial compared treatment with Velcade, thalidomide and dexamethasone (VcTD) to thalidomide and dexamethasone (TD) alone, in 256 patients with previously untreated MM.² The Italian Myeloma Network (GIMEMA) cooperative group conducted the trial. VcTD and TD were administered both pre- (as induction therapy) and post- double ASCT to patients with multiple myeloma. TD is currently the most common treatment for patients with previously untreated multiple myeloma.²

Induction therapy in both patient groups comprised three 21-day courses. Patients in the VcTD arm received 1.3mg/m² Velcade on days 1, 4, 8 and 11 of each cycle. These patients also received 200mg Thalidomide daily and 40mg Dexamethasone the day of and the day after Velcade administration. Patients in the TD arm received 200mg Thalidomide daily and 40 mg Dexamethosone on days 1-4 and 9-12 of each 21-day cycle. The primary endpoint of the study was complete response (CR) to the induction therapy. Secondary study endpoints included CR to consolidation therapy, time to disease progression (TTP), event-free survival (EFS), overall survival (OS) and toxicity.²

Patients administered the VcTD combination showed a CR rate of 36%, significantly higher (p<0.001) than 9% in the TD group. Post-ASCT the VcTD patient group demonstrated a CR rate of 57%, significantly higher again (p<0.001) than 28% in the TD group. ASCT was successful in more than 90% of patients in both treatment groups.²

Complete remission is widely seen as a strong predictor for long-term survival. The dramatic increase in complete remission rates seen in this study show that Velcade combination therapy can improve the complete remission rates of commonly used multiple myeloma treatments.

References

1. Rajkumar SV, Palumbo A. Management of newly diagnosed myeloma. Hematol Oncol Clin North Am. 2007 Dec;21(6):1141-56, ix-x.

2. PRESS RELEASE: Phase III Trial of VELCADE for injection Showed Dramatic Fourfold Increase in Complete Remission Rates [online]. 2008 [cited 31/01/08]. Available from: URL: http://www.fiercebiotech.com/press-releases/press-release-phase-iii-trial-velcade-injection-showed-dramatic-fourfold-increase-com

3. Harousseau JL, Shaughnessy J, Jr., Richardson P. Multiple myeloma. Hematology Am Soc Hematol Educ Program. 2004:237-56.

4. Blade J, Rosinol L. Complications of multiple myeloma. Hematol Oncol Clin North Am. 2007 Dec;21(6):1231-46, xi.

5. Gil L, Styczynski J, Dytfeld D, Debski R, Kazmierczak M, Kolodziej B, et al. Activity of bortezomib in adult de novo and relapsed acute myeloid leukemia. Anticancer Res. 2007 Nov-Dec;27(6B):4021-5.