Effects of long-term intravenous ibandronate therapy on skeletal-related events, survival, and bone resorption markers in patients with advanced multiple myeloma.
OBJECTIVE
Bisphosphonates have been found to reduce the incidence of skeletal-related events (SREs) in patients with multiple myeloma. This is the first double-blind, randomized, placebo-controlled study to assess the efficacy of ibandronate, a third-generation amino-bisphosphonate, in preventing SREs in advanced-stage multiple myeloma patients.


METHODS
Patients with multiple myeloma stage II or III were randomly assigned to receive either ibandronate 2 mg or placebo as a monthly intravenous (IV) bolus injection for 12 to 24 months in addition to conventional chemotherapy. SREs such as peripheral pathologic or vertebral fractures, hypercalcemia, severe bone pain, and bone radiotherapy or surgery were analyzed. Bone-turnover markers were also studied. Finally, post hoc analyses of bone morbidity and survival were performed.


RESULTS
Ninety-nine patients per treatment group were assessable for efficacy analysis. The occurrence of SRE per patient year and the time to first SRE were not significantly different between the two treatment groups. In overall evaluation, no differences were found between the treatment groups regarding bone pain, analgesic drug use, quality of life, and median survival (33.1 v 28.2 months, respectively). Explorative post hoc analyses revealed that ibandronate patients with strongly suppressed bone-turnover markers (> or = 30% and > or = 50% mean reduction of serum osteocalcin and urinary C-terminal telopeptides) developed significantly less bone morbidity. Ibandronate was tolerated well during as many as 25 therapy cycles.


CONCLUSIONS
Monthly injections of ibandronate 2 mg IV neither reduced bone morbidity nor prolonged survival in the overall population of stage II/III multiple myeloma patients.
Menssen
Hans D
HD
Department of Hematology and Oncology, Benjamin Franklin Klinik der Freien Universität, and St Hedwigs-Krankenhaus, Berlin, Germany. hmenssen@zedat.fu-berlin.de
Sakalová
Adriana
A
Fontana
Aurélie
A
Herrmann
Zuzana
Z
Boewer
Christian
C
Facon
Thierry
T
Lichinitser
Michail R
MR
Singer
C R J
CR
Euller-Ziegler
Liana
L
Wetterwald
Marc
M
Fiere
Denis
D
Hrubisko
Mikulás
M
Thiel
Eckhard
E
Delmas
Pierre D
PD
D001862:Bone Resorption / Q000209:etiology / Q000517:prevention & control; D016009:Chi-Square Distribution; D004164:Diphosphonates / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D050723:Fractures, Bone / Q000209:etiology / Q000517:prevention & control; D006801:Humans; D006934:Hypercalcemia / Q000209:etiology / Q000517:prevention & control; D000077557:Ibandronic Acid; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000150:complications* / Q000188:drug therapy* / Q000401:mortality; D010146:Pain / Q000209:etiology / Q000517:prevention & control; D013117:Spinal Cord Compression / Q000209:etiology / Q000517:prevention & control; D016019:Survival Analysis; D016896:Treatment Outcome
D004164:Diphosphonates; D000077557:Ibandronic Acid