TABLE V.

Results of studies of patients with multiple myeloma

Reference	Intervention	pfs (months)	Median ttp (months)	or (%)	cr (%)	Median os (months)	Median follow-up (months)
Previously untreated disease
Non-asct trials
San Miguel et al., 200824	Int: B–M–P	nr	24	71a	30a	ne	36.7/16.3b
	Control: M–P	nr	16.6	35a	4a	43%b
			hr: 0.48	p<0.001	p<0.001	hr: 0.61
			p<0.001c			p=0.008
Mateos et al., 201019	Induction: B–M–Pd	ns	ns	nsc	nr	ns	32
	Induction: B–T–P	ns	ns	nsc	nr	ns
	Maintenance: B–T	ns	nr	nr	nr	ns
	Maintenance: B–P	ns	nr	nr	nr	ns
Palumbo et al., 201021	Int: B–M–P–T plus B–Td	56%	nr	59	38	89%	23.2
	Control: B–M–P	41%	nr	50	24	87%
		hr: 0.67c		p=0.03	p<0.001	hr: 0.92
		p=0.008c				p=0.77
Niesvizky et al., 201182 (abs.)	B–T	13.8	nr	73	30	87.4%	21.8
	B–T–D	14.7	nr	80	40	86.1%
	B–M–P	17.3 (ns)	nr	69	33	88.9%
Kumar et al., 201226	B–D–C–L	86	nr	88	25	100%	20
	B–D–L	83	nr	85	24e	100%
	B–D–C	93	nr	75	22	100%
	B–D–C with C on day 15	100	nr	100	47	100%
asct trials
Cavo et al., 201015	B T D → double asct → B T D consolidation	68% (estimated at 3 years)	29%	nr	After induction: 44c	nsh	36
					After 1st asct: 89
					After 2nd asct: 98
					After consolidation: 116
					Overall treatment: 136
					p<0.0001
	D T → double asct → B T D consolidation	56%	39%	nr	After induction: 11	ns
		p=0.0057	p=0.0061		After 1st asct: 54 (p=0.0004)
		hr: 0.63			After 2nd asct: 72 (p=0.0105)
		(95% ci: 0.45 to 0.88, p=0.0061)			After consolidation: 82
						(p=0.0012)
						Overall treatment: 97
						p=0.0001
Harousseau et al., 201016	Int1: B–D and no consolidation	36.0	nr	After induction: 78.5	After induction: 14.8c,f	neg	32.2
	Int2: B–D plus D–C–E-Cis consolidation			p<0.001	p=0.004
	→ asct			After 1st transplant: ns	After 1st transplant: 16.1
					p=0.016
	Control1: V–Dox–D and no consolidation	29.7	nr	After induction: 62.8	After induction: 6.4	ned
	Control2: V–Dox–D plus D–C–E-Cis consolidation				After 1st transplant: 8.7
	→ asct	p=0.057
Moreau et al., 201128	B–D	30	nr	36	13	45%	32
	Reduced-dose B–T plus D	26 (ns)	nr	49 p=0.05	12 (ns)	53% (ns)
Rosinol et al., 201284 (abs.)	Maintenance: B–T	78	nr	nr	23	ns	24
	Maintenance: T	63	nr	nr	11	ns
	Maintenance: interferon	49	nr	nr	ns	ns
		p=0.01
Sharma et al., 201227	asct prep: M, ascorbic acid, ato plus B 1.0 mg/m2	17.8	nr	85	20c	nec	36
	asct prep: M, ascorbic acid, ato plus B 1.5 mg/m2	17.4	nr	90	10c	nec
	asct prep: M, ascorbic acid, ato	20.7	nr	95	10c	nec
						p=0.057
Sonneveld et al., 201231	Induction: B–Dox–D plus high-dose M, plus asct →	35	nr	nr	7→21	61%	41
	Maintenance: B Induction: V–Dox–D plus high-dose M, plus asct →	28	nr	nr	2→9	55%
	Maintenance: T	(p<0.002)			p<0.001	p=0.049
Relapsed or refractory disease
Richardson et al., 200523	B	nr	6.2c	38	6	29.8i	22
	D	nr	3.5c	18	1	23.7i
			hr: 0.55	p<0.001	p<0.001	hr: 0.77
			p<0.001			p=0.027
Orlowski et al., 200720	B	6.5	6.5c	41	2	65%	7.2g
	B plus peg-Dox	9.0	9.3c	44	4	76%
		hr: 1.69	hr: 1.82 (95% ci: 1.41 to 2.35)	p=0.43		(15 months)
		p=0.000026	p=0.000004			p=0.03
Lonial et al., 201017	B (escalating doses of 1.0, 1.3, and 1.6 mg/m 2) 24 hours before M	ns	nr	47	11	ns	17.3
	B (escalating doses of 1, 1.3, and 1.6 mg/m2) 24 hours after M	ns	nr	55	30	ns
Reece et al., 201122	B 1.3 mg/m2	nr	nr	52	5	nr	nr
	B 1.0 mg/m2	nr	nr	48	10	nr
Garderet et al., 201230	B–T–D	19.3	19.5	45	45	71%	30
	T–D	13.6	13.8	25	25	65%
		p<0.001	p<0.001	p<0.001	p<0.001	(ns)
Hjorth et al., 201225	B–D	7.2	1.6	63	nr	19	3.5 on B,
	T–D	9 (ns)	3.0	55 (ns)	nr	22.8	5.1 on Tj
			p<0.005
Orlowski et al., 201283 (abs.)	Siltuximab plus B	8.1	nr	55	11	30.8	24.5
	B	7.6 (ns)	nr	47 (ns)	7 (ns)	36.9 (ns)

^aResults in evaluable population (B–M–P: n = 337; M–P: n = 331).

^bMedian follow-up was 36.7 months for overall survival and 16.3 months for time to progression in the original publication. An update⁵⁵ confirmed a statistically significant survival benefit for B–M–P compared with M–P at a median follow-up of 25.9 months (hr: 0.64; p = 0.003). In a further publication⁵⁹, 3-year rates of overall survival were estimated at 68.5% for B–M–P compared with 54% with M–P.

^cResults for primary outcome.

^dBortezomib on a weekly schedule.

^eThe original data cut-off was April 28, 2006, at which time the median follow-up was 7.2 months; survival and time to event data were reanalyzed with a data cut-off of November 28, 2006, upon request by the U.S. Food and Drug Administration. Median follow-up for overall survival and time to progression were not reported.

^fResults in the evaluable population (B–D: n = 223 after induction, n = 197 after first transplant; V–Dox–D: n = 218 after induction, n = 184 after first transplant).

^gMedian overall has not been reached in either group. Overall survival rates were 81.4% with B–D and 81.4% with V–Dox–D.

^hThe estimated 3-year overall survival was 86% compared with 84% (p = 0.30).

ⁱData from an additional publication⁴¹.

^jTerminated early because of low accrual.

pfs = progression-free survival; ttp = time to progression; or = odds ratio; cr = complete response; os = overall survival; asct = autologous stem-cell transplantation; Int = intervention group; B = bortezomib; M = melphalan; P = prednisone; nr = not reported; hr = hazard ratio; ne = not reached or not estimable; T = thalidomide; ns = statistically nonsignificant; D = dexamethasone; C = cyclophosphamide; L = lenalidomide; abs. = abstract; E = etoposide; Cis = cisplatinum; V = vincristine; Dox = doxorubicin; ato = arsenic trioxide; peg-Dox = pegylated liposomal doxorubicin; ci = confidence interval.