SUBGROUP AND COST-BENEFIT-ANALYSIS OF THE FINNISH MULTICENTER TRIAL OF CLODRONATE IN MULTIPLE-MYELOMA

Osteolytic lesions and pathological fractures are the major problems i n the clinical management of multiple myeloma. We previously reported the main results of a randomized, controlled multicentre trial in 350 Finnish patients with multiple myeloma. All patients received standard melphalan-prednisolone treatment and were randomized to receive eithe r clodronate 2.4g daily or a placebo for 24 months. The proportion of patients with progression of osteolytic bone lesions was twice as high in the placebo group as in the clodronate group (24.0% v 12.0%, P = 0 .026). The purpose of the present study was to investigate factors ass ociated with the progression of osteolytic lesions and to identify sub groups of patients who would benefit most from clodronate treatment. I n univariate logistic regression analysis, including treatment (placeb o, clodronate), sex, age, pain index, serum calcium and creatinine, my eloma stage, number of osteolytic lesions at baseline, and number of v ertebral fractures at baseline as independent variables and the progre ssion of osteolytic lesions as a dependent variable, only the treatmen t with a placebo was associated with the progression of osteolytic bon e lesions. Separate analyses with respect to the progression of osteol ytic bone lesions were carried out in the following subgroups: male v female, less than or equal to 64 v > 64 years, stage I v stage II-III myeloma, no osteolytic lesions at baseline versus osteolytic lesions a t baseline, no vertebral fractures at baseline versus vertebral fractu res at baseline, and a 50% treatment response to cytotoxic drugs versu s no treatment response to cytotoxic drugs. The treatment with clodron ate delayed the progression of osteolytic lesions similarly in these s ubgroups, with the exception of a subgroup of patients who did not hav e a 50% treatment response to cytotoxic drugs. The treatment with clod ronate did not significantly increase treatment costs. We conclude tha t the treatment effect of clodronate seems to be independent of sex an d age of the patients, the stage of myeloma, and the severity of bone lesions at diagnosis, but not of treatment response to cytotoxic drugs .