Table 3.

Large Controlled Studies of BP Therapy in Multiple Myeloma

Controlled Trial	Year	BP	Dosage	MM (No. of patients)	Reduction of SREs*	Survival Benefit
Placebo
Lahtinen et al23	1992	CLO	2.4 g per day orally for 2 years	350	Yes	NE
Laakso et al24	1994
McCloskey et al13	1998	CLO	1.6 g per day orally	530	Yes	Subset†
McCloskey et al25	2001
Brincker et al26	1998	PAM	300 mg per day orally	300	No	No
Berenson et al27	1996	PAM	90 mg IV every 4 weeks for 21 cycles	392	Yes	Subset‡
Berenson et al28	1998
Menssen et al29	2002	IBN	2 mg IV once per month	198	No	No
PAM, 90 mg
Gimsing et al30	2010	PAM	30 v 90 mg IV every 4 weeks	504	Comparable	No change
Berenson et al31	2001	ZOL	2 or 4 mg IV once per month	108	Yes	NE
Rosen et al32	2001	ZOL	4 or 8 mg IV once per month	513	Yes	Subset§
Rosen et al33	2003
CLO, 1.6 g
Morgan et al34	2010	ZOL	4 mg IV every 3 to 4 weeks	1,960	Yes	Yes
Morgan et al35	2011
Morgan et al36	2012

NOTE. Data adapted.^19,30,34

Abbreviations: BP, bisphosphonate; CLO, clodronate; IBN, ibandronate; IV, intravenous; MM, multiple myeloma; NE, not evaluated; PAM, pamidronate; SRE, skeletal-related event; ZOL, zoledronic acid.

^*SREs include vertebral and nonvertebral fractures, need for radiation or surgery to bone, spinal cord compression.

^†In post hoc analysis, patients without vertebral fracture at study entry survived significantly longer with CLO (median survival, 23 months) compared with placebo.

^‡Survival in patients with more advanced disease was significantly increased in the PAM group (median survival, 21 v 14 months; P = .041, adjusted for baseline serum β₂-microglobulin and Eastern Cooperative Oncology Group performance status).

^§Survival benefit with ZOL over PAM in subgroup of patients who had elevated baseline bone-specific alkaline phosphatase levels.