(ChemotherapyAdvisor) – When administered during induction and as maintenance therapy in patients with newly diagnosed multiple myeloma, bortezomib improves complete response (CR) and achieves superior progression-free survival (PFS) and overall survival (OS), results of a randomized phase 3 trial reported in the Journal of Clinical Oncology online July 16.
The Dutch-Belgian Hemato-Oncology Cooperative Group (HOVOV-65)/German Multicenter Myeloma Group (GMMG-HD4) randomly assigned 827 patients with newly diagnosed symptomatic multiple myeloma to induction therapy with vincristine, doxorubicin, and dexamethasone (VAD) or bortezomib, doxorubicin, and dexamethasone (PAD), followed by high-dose melphalan and autologous stem cell transplantation. Thalidomide 50mg/day (VAD) or bortezomib 1.3mg/m2 (PAD) were administered as maintenance treatment once every 2 weeks for 2 years.
The investigators found CR, including near CR, was significantly greater following PAD induction (15% vs 31%; P<0.001) and bortezomib maintenance (34% vs 49%; P<0.001). After a median follow-up of 41 months, PFS was superior in the PAD arm; median 35 months compared with 28 months (HR 0.75; 95% CI, 0.62–0.90; P=0.002).
OS was found to be better in the PAD arm (HR, 0.77; 95% CI, 0.60–1.00; P=0.049) in multivariate analysis. Bortezomib significantly improved PFS from a median of 13 months to 30 months (HR 0.45; 95% CI, 0.26–0.78; P=0.004) and OS from a median of 21 months to 54 months (HR 0.33; 95% CI, 0.16 to 0.65; P=0.001) in high-risk patients who presented with increased creatinine more than 2mg/dL, they reported.
“A benefit was also observed in patients with deletion 17p13 (median PFS, 12 vs 22 months; HR, 0.47; 95% CI, 0.26–0.86; P<0.01; median OS, 24 months vs not reached at 54 months (HR 0.36; 95% CI, 0.18–0.74; P=0.003).
“Bortezomib-emergent peripheral neuropathy (BiPN) was the prevalent toxicity during induction, preventing a substantial number of patients from starting maintenance. In those who started maintenance, 5% experienced BiPN grade 3 to 4 toxicity. More patients were unable to complete thalidomide maintenance treatment. Hence, the lower percentage of failures in the bortezomib arm may have contributed to the better PFS/OS in that group. Prolonged administration of bortezomib in the once every 2 weeks schedule seems feasible, and therefore it is important to prevent BiPN during induction, enabling patients to continue into maintenance,” they wrote.
They noted the longer follow-up is warranted, since “a plateau in PFS and OS was not observed.”