Bortezomib Induction, Maintenance Improves Response, Survival in Patients with Newly Diagnosed Multiple Myeloma

Share this content:

(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.”


Related Resources

You must be a registered member of Cancer Therapy Advisor to post a comment.

Sign Up for Free e-newsletters

Regimen and Drug Listings


Bone Cancer Regimens Drugs
Brain Cancer Regimens Drugs
Breast Cancer Regimens Drugs
Endocrine Cancer Regimens Drugs
Gastrointestinal Cancer Regimens Drugs
Gynecologic Cancer Regimens Drugs
Head and Neck Cancer Regimens Drugs
Hematologic Cancer Regimens Drugs
Lung Cancer Regimens Drugs
Other Cancers Regimens
Prostate Cancer Regimens Drugs
Rare Cancers Regimens
Renal Cell Carcinoma Regimens Drugs
Skin Cancer Regimens Drugs
Urologic Cancers Regimens Drugs