Zoledronic acid reduces number of skeletal-related events in new multiple myeloma patients

Study Type: Therapy
OE Level of Evidence: 2
Journal Level of Evidence: N/A
Synopsis
1960 patients with multiple myeloma were randomized to undergo either intensive or non-intensive treatment. Within each treatment type patients were further randomized to receive either zoledronic acid intravenously or clodronic acid orally, in order to determine which bisphosphonate and treatment type was more effective in lowering the danger of skeletal-related events. Following assessments over Please login to view the rest of this report. Please login to view the rest of this report.
Funding: Non-Industry funded
Sponsor: Novartis, Schering Health Care, Chugai, Pharmion, Celgene, Ortho Biotech; Non-Industry Funded: Medical Research Council
Conflicts: None disclosed
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Why was this study needed now?
Patients with multiple myeloma go through bone destruction caused by the interaction between malignant plasma cells and bone marrow stromal cells that induce the synthesis of osteoclasts. Normally the damage produced by osteoclasts can be repaired by osteoblasts. However, myeloma cells have the ability to inhibit osteoblasts, thus preventing healing. Osteolysis can be treated with bisphosphonates, for instance clodronic acid, pamidronic acid, and zoledronic acid. This study aimed to compare how skeletal-related events were impacted by clodronic acid and zoledronic acid in patients who had been recently diagnosed with multiple myeloma.
What was the principal research question?
Are the skeletal-related events impacted differently by clodronic acid and zoledronic acid in patients who have been recently diagnosed with multiple myeloma, when measured over a minimum of 3 years?
Population: 1960 patients who were recently diagnosed with symptomatic multiple myeloma, which was confirmed through histological assessment (Age: >18)
Intervention: Clodronic Acid (Intensive Pathway) Group: Patients received intensive antimyeloma treatment and were administered 1600 mg of oral clodronic per day. Following this treatment, patients underwent maintenance therapy where they received 50 mg of thalidomide per day (Age: 59) (n=556) Zoledronic Acid (Intensive Pathway) Group: Patients received intensive antimyeloma treatment and were given 4 mg of zoledronic acid intravenously for 15 minute every 3-4 weeks with chemotherapy. Following this treatment, patients underwent maintenance therapy where they received 50 mg of thalidomide per day (Age: 59) (n=555)
Comparison: Clodronic Acid (Non-Intensive Pathway) Group: Patients received non-intensive antimyeloma treatment and were administered 1600 mg of oral clodronic per day. Following this treatment, patients underwent maintenance therapy where they received 50 mg of thalidomide per day (Age: 73) (n=423) Zoledronic Acid (Non-Intensive Pathway) Group: Patients received non-intensive antimyeloma treatment and were given 4 mg of zoledronic acid intravenously for 15 minute every 3-4 weeks with chemotherapy. Following this treatment, patients underwent maintenance therapy where they received 50 mg of thalidomide per day (Age: 73) (n=426)
Outcomes: The primary outcome measure was survival, progression-free survival, and the rate for the overall response to treatment. Secondary outcomes included occurrence of skeletal-related events (bone fracture, bone radiation, surgery required for bone lesions and spinal cord compression, height lost) and radiographs of the dorsal and lumbar spine
Methods: RCT: prospective; multi center
Time: Outcomes were measured at baseline and every 3 months following start of treatment. Median follow-up time was 3.7 years (Interquartile Range: 2.8-4.7 years)
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How will this affect the care of my patients?
The authors responsible for this critical appraisal and ACE Report indicate no potential conflicts of interest relating to the content in the original publication.