Abstract
A growing body of evidence is demonstrating that the nitrogen-containing bisphosphonate zoledronic acid (zol) improves clinical outcomes in various cancer settings, including multiple myeloma. Those findings provided the rationale for conducting an open-label randomized controlled phase iii trial to evaluate the effect of zol on overall survival (os) and progression-free survival (pfs) in patients with previously untreated high-risk multiple myeloma. The trial randomly assigned 308 adult patients less than 65 years of age with previously untreated symptomatic multiple myeloma (1:1) to receive zol 4 mg intravenously once every 28 days for 24 months (n = 151) or no zol (n = 157). Before autologous stem-cell transplantation (asct), all patients received a high-dose noncytotoxic induction regimen of dexamethasone, all-trans-retinoic acid, and interferon alpha 2b. After a median follow-up of 69.8 months (range: 36.5-96 months), the 10-year pfs (66% vs. 52%, p < 0.001) and os (67% vs. 48%, p < 0.001) rates were significantly higher in treated patients than in control patients. Overall response (77% zol vs. 75% control), complete response (52% vs. 46%), and very good partial response (25% vs. 29%) rates were similar between the groups. Treatment was generally well tolerated, with no reports of renal impairment or osteonecrosis of the jaw. In symptomatic previously untreated multiple myeloma patients, zol combined with high-dose therapy followed by asct improved os and pfs without appreciable toxicity. These findings provide additional evidence of the meaningful anticancer activity of zol in this patient population.
Highlights
Multiple myeloma is a plasma-cell malignancy that can cause osteolytic bone lesions, excess immunoglobulin secretion, renal impairment, and myelosuppression[1]
Overall response (77% zol vs. 75% control), complete response (52% vs. 46%), and very good partial response (25% vs. 29%) rates were similar between the groups
In symptomatic previously untreated multiple myeloma patients, zol combined with high-dose therapy followed by asct improved os and pfs without appreciable toxicity
Summary
Multiple myeloma is a plasma-cell malignancy that can cause osteolytic bone lesions, excess immunoglobulin secretion, renal impairment, and myelosuppression[1]. Just since the early 2000s, newly introduced therapies such as bortezomib, lenalidomide, and thalidomide have revolutionized the treatment paradigm in multiple myeloma and likely contributed to improved survival[2,3]. High-dose induction therapy with subsequent autologous stem-cell transplantation (asct) is the current standard of care for previously untreated patients with symptomatic multiple myeloma[4]. A growing body of evidence is demonstrating that the nitrogen-containing bisphosphonate zoledronic acid (zol) improves clinical outcomes in various cancer settings, including multiple myeloma. Those findings provided the rationale for conducting an open-label randomized controlled phase iii trial to evaluate the effect of zol on overall survival (os) and progression-free survival (pfs) in patients with previously untreated high-risk multiple myeloma
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