Summary of the 4 randomized clinical trials comparing different bisphosphonates and 1 study comparing zoledronate vs denosumab specifically in MM
| Trials . | Anti-MM treatment . | Type of bisphosphonate . | Number of patients . | Outcome measures . | ||||
|---|---|---|---|---|---|---|---|---|
| Other . | SRE . | Pain . | OS . | ONJ . | ||||
| Terpos et al 200382 | Vincristin-adriamycin-dexamethasone 4 cycles | Pamidronate IV vs ibandronate IV | 44 | More reduction in NTX and TRACP-5b with pamidronate | 86.9% vs 90.4% no progression of bone diseasea | NR | NR | NR |
| Rosen et al 200383b | NR | Zoledronate IV 4 mg and 8/4 mg vs pamidronate 90 mg IV every 3-4 wk for 24 mo | 1648; 1130 breast cancer and 518 MM | NR | 1.04 for 4 mg zoledronate vs 1.39 events/year for pamidronate (P = .084), no difference in MMc | NR | NR | NR |
| Gimsing et al 201084d | e | Pamidronate 90 mg vs 30 mg IV | 504 | Similar improvement in physical function | 34% vs 36% patientsf | Similar improvement in pain | 3 vs 0.8%g | |
| Morgan et al 201085h | i | Zoledronate 4 mg IV every 3-4 wk vs 1600 mg/d clodronate | 1960 | NR | 27 vs 35% before disease progression; P = .004j | NR | HR, 0.84; 95% CI 0.74-0.96; P = .0118 | 4 vs 1% |
| Raje et al 201886 | k | Zoledronate vs denosumab | 1718 | NR | 45 vs 44% on study | HR, 0.90; 95% CI 0.70-1.16, P = .41 | 3 vs 4% renal toxicity 17 vs 10% | |
| Trials . | Anti-MM treatment . | Type of bisphosphonate . | Number of patients . | Outcome measures . | ||||
|---|---|---|---|---|---|---|---|---|
| Other . | SRE . | Pain . | OS . | ONJ . | ||||
| Terpos et al 200382 | Vincristin-adriamycin-dexamethasone 4 cycles | Pamidronate IV vs ibandronate IV | 44 | More reduction in NTX and TRACP-5b with pamidronate | 86.9% vs 90.4% no progression of bone diseasea | NR | NR | NR |
| Rosen et al 200383b | NR | Zoledronate IV 4 mg and 8/4 mg vs pamidronate 90 mg IV every 3-4 wk for 24 mo | 1648; 1130 breast cancer and 518 MM | NR | 1.04 for 4 mg zoledronate vs 1.39 events/year for pamidronate (P = .084), no difference in MMc | NR | NR | NR |
| Gimsing et al 201084d | e | Pamidronate 90 mg vs 30 mg IV | 504 | Similar improvement in physical function | 34% vs 36% patientsf | Similar improvement in pain | 3 vs 0.8%g | |
| Morgan et al 201085h | i | Zoledronate 4 mg IV every 3-4 wk vs 1600 mg/d clodronate | 1960 | NR | 27 vs 35% before disease progression; P = .004j | NR | HR, 0.84; 95% CI 0.74-0.96; P = .0118 | 4 vs 1% |
| Raje et al 201886 | k | Zoledronate vs denosumab | 1718 | NR | 45 vs 44% on study | HR, 0.90; 95% CI 0.70-1.16, P = .41 | 3 vs 4% renal toxicity 17 vs 10% | |
Follow-up, 10 months.
Follow-up, 25 months.
Defined as pathological fracture, spinal cord compression, need for radiation, or surgery to bone lesions.
Median follow-up, 3.4 years.
Melphalan and prednisone with or without thalidomide (n = 213), vincristine, doxorubicin, and dexamethasone or cyclophosphamide and dexamethasone, followed by high-dose melphalan and auSCT (n = 289).
First SREs were vertebral fractures (n = 38 vs n = 40), surgically treated nonvertebral fractures (5 patients in each group), irradiated osteolytic lesions (n = 14 vs n = 12), new symptomatic osteolytic lesions (n = 27 vs n = 28), and hypercalcemia (1 patient vs 5 patients).
Retrospective analysis.
Median follow up, 3.7 years.
Induction therapies: cyclophosphamide-vincristine-doxorubicin-dexamethasone or cyclophosphamide-thalidomide-dexamethasone (CTD) followed by high-dose therapy plus auSCT for younger/fitter patients (intensive pathway) and melphalan-prednisone or attenuated CTD for older/less fit patients (nonintensive pathway).
Defined as vertebral fractures, other fractures, spinal cord compression, need for radiation or surgery to bone lesions, and new osteolytic bone lesions recorded until disease progression.
Fifty-two percent treated with a PI, 17% with an immunomodulatory drug, 27% both, and 4% other.
NTX, N-terminal crosslinking telopeptide of type-I collagen, a bone resorption marker; ONJ, osteonecrosis of the jaw; TRACP-5b, tartrate-resistant acid phosphatase type 5b.