A retrospective study of skeletal and disease-free survival benefits of zoledronic acid therapy in patients with multiple myeloma treated with novel agents

Background: The large majority of patients with multiple myeloma develop bone lesions and typically receive bisphosphonates to maintain bone health and prevent/delay skeletal-related events. Recent clinical data show that the newer-generation bisphosphonate, zoledronic acid, may confer a survival benefit when combined with antimyeloma therapy. However, clinical data describing the combination of zoledronic acid with newer antimyeloma regimens are limited. Design and Methods: This retrospective study analyzed efficacy and safety outcomes in patients with multiple myeloma receiving first- and second-line treatment with bortezomib, lenalidomide, or thalidomide, with or without zoledronic acid. Results: Records data from 94 patients with Durie-Salmon stage 3A/B multiple myeloma were collated. Most patients (~80%) had bone lesions at study entry. Almost all patients received zoledronic acid at some time during their treatment. Adding zoledronic acid was associated with a numerical, but statistically nonsignificant, benefit in the 1-year progression-free survival rate in both the first- and second-line setting. A similar benefit was observed on the 2-year skeletal-related event rate. Notably, combining zoledronic acid with newer antimyeloma agents was feasible, tolerable, and did not affect the duration of antimyeloma treatment. Three cases of osteonecrosis of the jaw were reported; there were no reports of acute renal failure. Conclusions: This retrospective analysis suggests that extended treatment with zoledronic acid in combination with bortezomib, lenalidomide, or thalidomide is safe and tolerable in patients receiving these therapies as first- or second-line treatment. The addition of zoledronic acid may improve both myeloma and skeletal-related outcomes.