Prolonged Use of Zoledronic Acid (4 Years) Did Not Improve Outcome in Multiple Myeloma Patients

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To assess whether prolonged use of zoledronic acid (ZA; 4 years) improves outcome in multiple myeloma patients, we performed a clinical trial to compare the effect of 48 and 24 months of treatment. A total of 170 patients were randomly assigned to the 2 groups in the trial. Overall survival was not improved, however, the ZA group showed a reduced number of skeletal events. Thus, we suggest that ZA should be considered to be used for longer duration, in an attempt to improve patient quality of life.


Bisphosphonates, especially zoledronic acid (ZA), show antitumor effects in multiple myeloma (MM) and other neoplasms. The standard time for ZA administration has been 2 years. However, with improvement in overall survival (OS) in MM with new agents, it unclear whether ZA could be administered for a prolonged time to improve OS.

Patients and Methods:

A total of 170 patients with untreated, symptomatic MM were randomly divided into a group to receive ZA for 4 years, with a control group to receive ZA for 2 years. All patients were treated with the same induction therapy and stem-cell transplantation.


Actuarial curves at 5 years, showed that progression-free survival was 75% (95% confidence interval [CI], 64%-82%) and OS was 68% (95% CI, 60%-76%) in the 4-year group, which was not statistically significantly different compared with the control group: 72% (95% CI, 62%-78%) and 68% (95% CI, 60%-75%; P = .67). However, the 4-year group showed reduced skeletal events (21% occurrence rate); this was statistically significant compared with the control group: 43% (P < .001).


Although ZA did not improve OS in patients with MM; it continued to be useful to reduce skeletal events, and thus improve better quality of life for patients.

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