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Chapter 86 Plasma Cell Neoplasms 1417

Clochonic acid + Censored
40 Zoledronic acid 35% 100 = .0107
2
90
Patients with skeletal- related events (%) 20 HR-0.74 (95% Cl, 0.62-0.87); 27% Overall survival (% patients) 70 CLO (n = 682)
HR = 0.82 (0.6% Cl, 0.70, 0.06)
80
30
60
50
40
30
10
10
0 P = .0004 20 0 ZOL (n = 668)
0 6 21 18 24 30 36 42 0 1 2 3 4 5
A Time from randomization (mo) D Survival since initial randomization (yr)
Number at risk
Clochonic acid 979 629 465 337 256 173 112 74 ZOL 668 544 447 292 165 64
Zoledronic acid 0.5 981 663 506 390 284 201 138 97 CLO 100 662 534 + Censored 143 53
437
271
Cumulative incidence function, skeletal-related events (%) 0.4 HR-0.77 (95% Cl, HR, 0.53 (95% Cl, Overall survival (% patients) 90 CLO (n = 276)
2
= .4690
HR = 1.10 (95% Cl, 0.85, 1.60)
80
0.33-0.84)
70
log-rank P = .0068
60
0.3
50
40
0.2
30
20
0.65-0.92)
0.1
ZOL (n = 302)
10
log-rank P = .0038
0
0 6 121824303642485460
Survival since initial randomization (yr)
Time from randomization 0 6 121824303642485460 0 0 1 2 3 4 5
Time from randomization
B (mo) C (mo) E
Fig. 86.17 Time to first skeletal-related event overall (A), in patients with bone lesions at baseline (B), and
in patients without bone lesions at baseline (C). Cox proportional hazards p-value. Kaplan-Meier analyses of
OS with zoledronic acid (ZOL) versus Clodronate (CLO) in patients with or without bone disease or other
SRE at baseline. (D) Patients with bone disease or other SRE at baseline. (E) Patients without bone disease
or other SRE at baseline. The benefit appears to be predominantly in those with prior SREs. CI, Confidence
interval; CLO, clodronate; HR, hazard ratio; OS, overall survival; SRE, skeletal-related event; ZOL, zoledronic
acid. (Adapted from Morgan GJ, Child JA, Gregory WM, et al: Effects of zoledronic acid versus clodronic acid on skeletal
morbidity in patients with newly diagnosed multiple myeloma (MRC Myeloma IX): Secondary outcomes from a randomised
controlled trial. Lancet Oncol 12:743, 2011; Morgan GJ, Davies FE, Gregory WM, et al: Effect of induction and
maintenance plus long-term bisphosphonates on bone disease in patients with multiple myeloma: the Medical Research
Council Myeloma IX trial. Blood 119:5374, 2012.)
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