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Zoledronate for early-stage, untreated myeloma: An interim report of a randomized study.

6680 Background: We have recently demonstrated that "prophylactic" administration of pamidronate is not useful to prevent or delay disease progression in patients with untreated, early-stage myeloma, although this treatment may reduce the number of cases developing skeletal events, thus possibly changing the clinical manifestations of the disease at progression (Musto et al, Leuk Lymphoma 2003; 44: 1545 and J Clin Oncol 2003; 21: 3177). No data are available about the effect of zoledronate (ZOL), a third generation bisphosphonate, in this specific setting of patients.


METHODS
Starting on June, 2001, all our patients with asymptomatic monoclonal gammopathy, fulfilling the diagnostic criteria of stage IA, IIA or "smouldering" myeloma, are invited to participate into an on-going clinical, randomized trial comparing one-year administration of ZOL alone vs simple observation. The aim of this study was to establish whether ZOL may modify the natural history of the disease, in terms of rate, time and type of progression, in these otherwise untreated patients. As of December, 2003, sixty-two patients, out of a planned accrual of 120 patients, have been randomized (thrity-one per arm) to receive or not ZOL (Zometa, Novartis Pharmaceuticals. Origgio, Italy) for one year or until progression, on an out-patient basis, at the dose of 4 mg as 15' i.v. single monthly infusion.


RESULTS
No significant adverse events have been so far recorded. In the observational arm two patients were lost at follow-up after six and twenty months, respectively. Asymptomatc hypocalcemia occurred in four of ZOL-treated patiens. After a median follow-up of 17 months there have been three (9.6%) progressions requiring treatment in the ZOL group and five (17.2%) within the controls (p.n.s.). Median time-to-progression was 17 and 14.3 months, respectively (p.n.s.). Bone lesions and/or hypercalcemia at the time of progression were observed in 4/5 of controls, and in 1/3 of ZOL-treated patients.


CONCLUSIONS
In this interim analysis, a moderate trend in favour of ZOL-arm was seen. The final evaluation of our trial, including a larger number of patients with prolonged follow-up, is required to clarify whether the use of ZOL may be clinically useful in initial stages of myeloma. No significant financial relationships to disclose.