Efficacy of maintenance treatment in patients with multiple myeloma: a systematic review and network meta-analysis

Figures & data

Figure 1. PRISMA flowchart illustrating the selection of studies included in our analyses.

Figure 2. Results of risk of bias assessment.

Table 1. Baseline characteristics of the studies included in this NMA.

Auther	Year	number of patients	Maintenance	Dose	median age	outcome	ASCT
Attal et al. [6]	2012	307 vs 307	lenalidomide vs Placebo	lenalidomide: 10 mg per day, increased to 15 mg if tolerated, days 1–21	55 vs 55	PFS, OS	Yes
Dimopoulos et al. [7]	2020	425 vs 281	ixazomib vs Placebo	ixazomib:3 mg, on days 1, 8, and 15 of 28-day cycles	72 vs 73	PFS	No
Zeegman et al. [8]	2020	39 vs 39	ixazomib vs Placebo	ixazomib 4 mg day 1, 8 and 15 of a 28-day cycle	72 vs 73	PFS, OS	No
Morgan et al. [9]	2013	408 vs 410	Thal vs Placebo	50 mg/d for 4 weeks, increasing to 100 mg/d if well tolerated	65 vs 64	PFS, OS	Mixed
Jackson et al. [10]	2020	406 vs 317	Len vs Placebo	Lenalidomide: 10 mg per day, days 1–21 vs placebo	61 vs 61	PFS, OS	Yes
Rosiñol et al. [11]	2017	56 vs 55 vs 59	BortThal vs Thal vs IFN	thalidomide 100 mg per day orally plus bortezomib on days 1, 4, 8 and 11 vs. Thal:100 mg per day vs. IFN 1.5 MU subcutaneously three times per week	56 vs 55 vs 59	PFS, OS	Yes
Dimopoulos et al. [12]	2018	395 vs 261	ixazomib vs Placebo	ixazomib:3 mg on days 1, 8, and 15 in 28-day cycles, Dose increased to 4 mg from cycle 5 vs placebo	58 vs 60	PFS	Yes
Gay et al. [13]	2015	117 vs 106	LenPred vs Len	lenalidomide 10 mg, days 1–21 plus prednisone 50 mg, every other day vs lenalidomide 10 mg, days 1–21	57 vs 56	PFS, OS	Yes
Holstein et al. [14]	2017	231 vs 229	Len vs Placebo	lenalidomide 10 mg, days 1–21 vs placebo		PFS, OS	Yes
Gay et al [15]	2021	178 vs 178	CarfilzomibLen vs Len	carfilzomib 36 mg/m^2 was administered intravenously on days 1–2 and 15–16 every 28 days plus lenalidomide 10 mg, days 1–21 vs lenalidomide 10 mg days 1–21	56 vs 57	PFS	Yes
Bringhen et al. [16]	2020	198 vs 204	LenPred vs Len	lenalidomide 10 mg/day days 1–21 plus prednisone 25 mg every other day vs lenalidomide 10 mg days 1–21		PFS	No
Moreau et al. [17]	2021	442 vs 444	Daratumumab vs Placebo	daratumumab 16 mg/kg intravenously every 8 weeks vs placebo	59 vs 59	PFS	Yes
Donk et al. [18]	2018	268 vs 268	Thal vs IFN	thalidomide 50 mg daily vs placebo	59 vs 58	PFS, OS	Yes
Ludwig et al. [19]	2010	64 vs 64	ThalIFN vs IFN	thalidomide 200 mg The median daily dose of thalidomide was 75 mg (range 25-200 mg) plus interferon: 3 Mega U, TIW vs interferon: 3 Mega U, TIW	71 vs 72	PFS, OS	No
Mareos et al. [20]	2012	91 vs 87	BortThal vs BortPred	bortezomib 1.3 mg/m2 on days 1, 4, 8, and 11 plus thalidomide 50 mg per day vs bortezomib 1.3 mg/m2 on days 1, 4, 8, and 11 plus prednisone 50 mg every other day	71 vs 72	PFS, OS	No
Palumbo et al. [21]	2014	126 vs 125	Len vs Placebo	lenalidomide 10 mg per day vs plavebo		PFS, OS	Yes
Brioli et al. [22]	2019	19 vs 21	Len vs Placebo	lenalidomide 10 mg per day vs plavebo	73 vs 76	PFS, OS	No
Mateos et al. [23]	2019	350 vs 356	Daratumumab vs Placebo	daratumumab 16 mg/kg, every 4 weeks		PFS, OS	No
Palumbo et al. [24]	2012	152 vs 153	Len vs Placebo	lenalidomide 10 mg per day vs plavebo	71 vs 71	PFS, OS	No

CarfilzomibLen: Carfilzomib-lenalidomide; BortThal: bortezomib-thalidomide; IFN: interferon; LenPred: lenalidomide-prednisone; Thal: thalidomide; ThalIFN: thalidomide- interferon.

Table 2. Matrix of pairwise comparisons of regimens on 6 months OS rate (shown as odds ratios and 95% confidence intervals).

	A	I	D	B	H	G	C	F	E
SUCRA (%)	72.1	70.3	63.9	58.2	56.1	39.2	38	33.4	18.8
A	A	0.48 (0.04,5.37)	0.73 (0.02,24.31)	0.50 (0.04,6.73)	0.79 (0.11,5.54)	0.36 (0.03,4.39)	0.33 (0.03,3.23)	0.22 (0.00,10.62)	0.20 (0.01,2.94)
I	2.09 (0.19,23.48)	I	0.72 (0.01,34.26)	0.49 (0.02,10.57)	0.47 (0.03,8.69)	0.35 (0.02,7.00)	0.32 (0.03,3.19)	0.22 (0.00,14.50)	0.20 (0.01,4.57)
D	1.37 (0.04,45.52)	1.40 (0.03,66.96)	D	0.68 (0.05,8.60)	0.65 (0.05,8.27)	0.49 (0.04,5.60)	0.45 (0.02,10.20)	0.30 (0.01,13.89)	0.27 (0.02,3.77)
B	2.01 (0.15,27.12)	2.05 (0.09,44.47)	1.47 (0.12,18.52)	B	0.96 (0.37,2.52)	0.71 (0.36,1.41)	0.66 (0.08,5.16)	0.45 (0.02,9.11)	0.40 (0.13,1.29)
H	1.27 (0.18,8.92)	2.14 (0.12,39.69)	1.53 (0.12,19.32)	1.04 (0.40,2.73)	H	0.74 (0.38,1.47)	0.69 (0.11,4.23)	0.46 (0.02,9.50)	0.42 (0.13,1.35)
G	2.81 (0.23,34.68)	2.87 (0.14,57.70)	2.05 (0.18,23.63)	1.40 (0.71,2.76)	1.34 (0.68,2.66)	G	0.93 (0.13,6.44)	0.62 (0.03,11.80)	0.56 (0.22,1.45)
C	3.03 (0.31,29.70)	3.10 (0.31,30.61)	2.22 (0.10,50.10)	1.51 (0.19,11.78)	1.45 (0.24,8.89)	1.08 (0.16,7.49)	C	0.67 (0.02,22.77)	0.61 (0.07,5.26)
F	4.51 (0.09,215.50)	4.60 (0.07,307.22)	3.29 (0.07,150.54)	2.24 (0.11,45.88)	2.15 (0.11,44.07)	1.60 (0.08,30.33)	1.49 (0.04,50.27)	F	0.91 (0.06,14.65)
E	4.98 (0.34,72.92)	5.09 (0.22,118.15)	3.64 (0.27,49.92)	2.48 (0.77,7.94)	2.38 (0.74,7.64)	1.77 (0.69,4.55)	1.64 (0.19,14.18)	1.10 (0.07,17.89)	E

Abbreviation: A = BortThal, B = Daratumumab, C = IFN, D = Ixazomib, E = Len, F = LenPred, G = Placebo, H = Thal, I = ThalIFN.

BortThal: bortezomib-thalidomide; IFN: interferon; LenPred: lenalidomide- prednisone; Thal: thalidomide; ThalIFN: thalidomide- interferon.

Table 3. Matrix of pairwise comparisons of regimens on 12 months OS rate (shown as odds ratios and 95% confidence intervals).

	A	D	B	H	E	I	G	F	C
SUCRA (%)	73.8	67.6	62.2	54.1	48.1	45	41.6	31.9	25.8
A	A	0.86 (0.03,27.46)	0.54 (0.04,6.82)	0.69 (0.11,4.17)	0.44 (0.03,5.60)	0.48 (0.04,5.36)	0.42 (0.04,4.89)	0.24 (0.01,8.06)	0.24 (0.03,2.23)
D	1.17 (0.04,37.53)	D	0.64 (0.05,7.82)	0.56 (0.05,6.73)	0.52 (0.04,6.42)	0.44 (0.02,12.03)	0.49 (0.04,5.60)	0.28 (0.01,9.29)	0.29 (0.01,5.90)
B	1.84 (0.15,22.97)	1.57 (0.13,19.26)	B	0.88 (0.42,1.83)	0.81 (0.35,1.87)	0.70 (0.07,6.87)	0.76 (0.43,1.34)	0.44 (0.03,5.73)	0.45 (0.07,2.92)
H	1.45 (0.24,8.72)	1.79 (0.15,21.53)	1.14 (0.55,2.38)	H	0.93 (0.43,2.01)	0.79 (0.09,6.94)	0.87 (0.54,1.39)	0.51 (0.04,6.40)	0.51 (0.09,2.87)
E	2.26 (0.18,28.61)	1.93 (0.16,24.00)	1.23 (0.53,2.84)	1.08 (0.50,2.34)	E	0.86 (0.09,8.57)	0.94 (0.51,1.74)	0.55 (0.05,6.13)	0.55 (0.08,3.65)
I	2.09 (0.19,23.47)	2.25 (0.08,61.08)	1.44 (0.15,14.16)	1.26 (0.14,11.01)	1.17 (0.12,11.65)	I	1.10 (0.12,10.08)	0.64 (0.02,17.95)	0.64 (0.17,2.40)
G	2.40 (0.20,28.19)	2.05 (0.18,23.63)	1.31 (0.74,2.30)	1.15 (0.72,1.84)	1.06 (0.57,1.97)	0.91 (0.10,8.38)	G	0.58 (0.05,7.03)	0.59 (0.10,3.50)
F	4.13 (0.12,137.16)	3.53 (0.11,115.67)	2.25 (0.17,28.94)	1.97 (0.16,24.92)	1.83 (0.16,20.43)	1.57 (0.06,44.03)	1.72 (0.14,20.77)	F	1.01 (0.05,21.65)
C	4.09 (0.45,37.28)	3.50 (0.17,72.10)	2.23 (0.34,14.50)	1.95 (0.35,10.95)	1.81 (0.27,11.97)	1.55 (0.42,5.78)	1.70 (0.29,10.16)	0.99 (0.05,21.26)	C

Abbreviation: A = BortThal, B = Daratumumab, C = IFN, D = Ixazomib, E = Len, F = LenPred, G = Placebo, H = Thal, I = ThalIFN.

BortThal: bortezomib-thalidomide; IFN: interferon; LenPred: lenalidomide- prednisone; Thal: thalidomide; ThalIFN: thalidomide- interferon.

Table 4. Matrix of pairwise comparisons of regimens on 18 months OS rate (shown as odds ratios and 95% confidence intervals).

	F	E	A	D	I	B	H	C	G
SUCRA (%)	82.8	70.4	56.1	53.6	43.6	40.5	39.9	32.6	30.4
F	F	0.59 (0.14,2.48)	0.47 (0.04,5.10)	0.46 (0.04,5.58)	0.34 (0.03,4.17)	0.34 (0.06,1.95)	0.34 (0.06,1.89)	0.28 (0.03,2.71)	0.30 (0.06,1.42)
E	1.69 (0.40,7.12)	E	0.79 (0.12,5.36)	0.77 (0.10,6.02)	0.57 (0.07,4.51)	0.58 (0.21,1.56)	0.57 (0.22,1.49)	0.47 (0.08,2.77)	0.50 (0.27,0.95)
A	2.13 (0.20,23.25)	1.26 (0.19,8.50)	A	0.98 (0.07,13.85)	0.72 (0.14,3.72)	0.73 (0.10,5.13)	1.07 (0.20,5.69)	0.59 (0.12,2.90)	0.63 (0.10,3.83)
D	2.19 (0.18,26.70)	1.29 (0.17,10.02)	1.02 (0.07,14.54)	D	0.74 (0.05,11.74)	0.74 (0.09,6.03)	0.73 (0.09,5.87)	0.61 (0.05,7.82)	0.65 (0.09,4.55)
I	2.97 (0.24,36.65)	1.75 (0.22,13.80)	1.40 (0.27,7.25)	1.36 (0.09,21.57)	I	1.01 (0.12,8.30)	0.99 (0.16,6.17)	0.82 (0.28,2.39)	0.88 (0.12,6.27)
B	2.94 (0.51,16.86)	1.74 (0.64,4.69)	1.38 (0.19,9.74)	1.34 (0.17,10.91)	0.99 (0.12,8.17)	B	0.99 (0.34,2.83)	0.82 (0.13,5.05)	0.87 (0.41,1.87)
H	2.98 (0.53,16.80)	1.76 (0.67,4.62)	0.94 (0.18,5.00)	1.36 (0.17,10.90)	1.01 (0.16,6.24)	1.01 (0.35,2.91)	H	0.83 (0.19,3.66)	0.88 (0.43,1.83)
C	3.60 (0.37,35.13)	2.12 (0.36,12.47)	1.69 (0.34,8.25)	1.65 (0.13,21.17)	1.21 (0.42,3.51)	1.22 (0.20,7.55)	1.21 (0.27,5.32)	C	1.07 (0.20,5.57)
G	3.37 (0.70,16.20)	1.99 (1.05,3.76)	1.58 (0.26,9.56)	1.54 (0.22,10.82)	1.14 (0.16,8.11)	1.15 (0.53,2.46)	1.13 (0.55,2.34)	0.94 (0.18,4.89)	G

Abbreviation: A = BortThal, B = Daratumumab, C = IFN, D = Ixazomib, E = Len, F = LenPred, G = Placebo, H = Thal, I = ThalIFN.

BortThal: bortezomib-thalidomide; IFN: interferon; LenPred: lenalidomide- prednisone; Thal: thalidomide; ThalIFN: thalidomide- interferon.

Table 5. Matrix of pairwise comparisons of regimens on 24 months OS rate (shown as odds ratios and 95% confidence intervals).

	F	G	C	J	E	H	B	A	D	I
SUCRA (%)	82.4	77	71.5	46.5	26.2	43.1	40.2	33.3	30.5	29.3
F	F	1.00 (0.41,2.47)	0.84 (0.48,1.45)	0.61 (0.22,1.73)	0.56 (0.14,2.23)	0.56 (0.38,0.82)	0.52 (0.17,1.64)	0.46 (0.11,1.82)	0.47 (0.25,0.90)	0.47 (0.28,0.78)
G	1.00 (0.41,2.45)	G	0.83 (0.29,2.39)	0.61 (0.15,2.41)	0.56 (0.11,2.90)	0.56 (0.21,1.48)	0.52 (0.12,2.23)	0.46 (0.09,2.37)	0.47 (0.16,1.43)	0.47 (0.17,1.32)
C	1.20 (0.69,2.07)	1.20 (0.42,3.44)	C	0.73 (0.26,2.08)	0.67 (0.17,2.67)	0.67 (0.45,0.99)	0.62 (0.20,1.97)	0.55 (0.14,2.19)	0.57 (0.29,1.09)	0.56 (0.33,0.95)
J	1.63 (0.58,4.60)	1.64 (0.42,6.47)	1.37 (0.48,3.88)	J	0.91 (0.18,4.72)	0.91 (0.35,2.40)	0.85 (0.23,3.14)	0.75 (0.16,3.40)	0.77 (0.34,1.74)	0.77 (0.31,1.90)
E	1.79 (0.45,7.11)	1.79 (0.35,9.32)	1.49 (0.37,5.97)	1.09 (0.21,5.65)	E	1.00 (0.27,3.77)	0.93 (0.17,5.16)	0.82 (0.12,5.35)	0.85 (0.20,3.53)	0.84 (0.21,3.32)
H	1.79 (1.22,2.61)	1.79 (0.68,4.76)	1.49 (1.01,2.22)	1.09 (0.42,2.87)	1.00 (0.27,3.77)	H	0.93 (0.32,2.75)	0.82 (0.22,3.09)	0.85 (0.50,1.43)	0.84 (0.60,1.18)
B	1.92 (0.61,6.01)	1.92 (0.45,8.24)	1.60 (0.51,5.06)	1.17 (0.32,4.31)	1.07 (0.19,5.93)	1.07 (0.36,3.15)	B	0.88 (0.40,1.90)	0.91 (0.33,2.51)	0.90 (0.32,2.51)
A	2.19 (0.55,8.70)	2.19 (0.42,11.41)	1.83 (0.46,7.32)	1.34 (0.29,6.09)	1.22 (0.19,8.00)	1.22 (0.32,4.62)	1.14 (0.53,2.48)	A	1.04 (0.29,3.73)	1.03 (0.29,3.72)
D	2.11 (1.11,4.02)	2.12 (0.70,6.41)	1.76 (0.92,3.40)	1.29 (0.57,2.91)	1.18 (0.28,4.91)	1.18 (0.70,1.99)	1.10 (0.40,3.05)	0.96 (0.27,3.47)	D	0.99 (0.67,1.47)
I	2.12 (1.27,3.53)	2.13 (0.76,5.99)	1.78 (1.05,2.99)	1.30 (0.53,3.20)	1.19 (0.30,4.68)	1.19 (0.84,1.67)	1.11 (0.40,3.08)	0.97 (0.27,3.50)	1.01 (0.68,1.49)	I

Abbreviation: A = BortPred, B = BortThal, C = Daratumumab, D = IFN, E = Ixazomib, F = Len, G = LenPred, H = Placebo, I = Thal, J = ThalIFN.

BortThal: bortezomib-thalidomide; IFN: interferon; LenPred: lenalidomide- prednisone; Thal: thalidomide; ThalIFN: thalidomide- interferon.

Table 6. Matrix of pairwise comparisons of regimens on 30 months OS rate (shown as odds ratios and 95% confidence intervals).

	G	F	C	E	B	H	J	D	I	A
SUCRA (%)	82.4	77.5	68.8	56.7	49.8	41.3	39.1	32.3	31	21
G	G	0.81 (0.33,1.98)	0.71 (0.25,2.06)	0.63 (0.12,3.17)	0.52 (0.12,2.27)	0.51 (0.19,1.34)	0.45 (0.09,2.30)	0.41 (0.10,1.73)	0.44 (0.16,1.26)	0.32 (0.06,1.66)
F	1.23 (0.50,3.00)	F	0.88 (0.50,1.55)	0.77 (0.20,2.99)	0.64 (0.20,2.06)	0.62 (0.42,0.92)	0.55 (0.14,2.17)	0.51 (0.17,1.56)	0.55 (0.32,0.94)	0.40 (0.10,1.56)
C	1.40 (0.49,4.05)	1.14 (0.64,2.02)	C	0.88 (0.22,3.44)	0.73 (0.23,2.38)	0.71 (0.47,1.08)	0.63 (0.16,2.50)	0.58 (0.19,1.80)	0.62 (0.35,1.10)	0.46 (0.11,1.80)
E	1.60 (0.32,8.09)	1.30 (0.33,5.03)	1.14 (0.29,4.47)	E	0.84 (0.15,4.58)	0.81 (0.22,2.97)	0.71 (0.11,4.54)	0.66 (0.12,3.52)	0.71 (0.18,2.74)	0.52 (0.08,3.28)
B	1.91 (0.44,8.25)	1.55 (0.49,4.95)	1.36 (0.42,4.40)	1.19 (0.22,6.54)	B	0.97 (0.32,2.89)	0.85 (0.24,3.07)	0.79 (0.29,2.16)	0.85 (0.30,2.36)	0.62 (0.30,1.27)
H	1.97 (0.75,5.22)	1.61 (1.09,2.36)	1.41 (0.92,2.15)	1.24 (0.34,4.53)	1.03 (0.35,3.09)	H	0.88 (0.24,3.30)	0.82 (0.29,2.34)	0.88 (0.60,1.29)	0.64 (0.17,2.37)
J	2.24 (0.43,11.52)	1.82 (0.46,7.19)	1.60 (0.40,6.37)	1.40 (0.22,8.92)	1.17 (0.33,4.22)	1.13 (0.30,4.24)	J	0.93 (0.42,2.06)	0.99 (0.28,3.50)	0.73 (0.21,2.56)
D	2.41 (0.58,10.10)	1.96 (0.64,6.01)	1.72 (0.55,5.35)	1.51 (0.28,8.04)	1.27 (0.46,3.45)	1.22 (0.43,3.50)	1.08 (0.49,2.39)	D	1.07 (0.40,2.85)	0.78 (0.23,2.69)
I	2.26 (0.79,6.42)	1.83 (1.06,3.16)	1.61 (0.91,2.85)	1.41 (0.36,5.48)	1.18 (0.42,3.30)	1.14 (0.78,1.68)	1.01 (0.29,3.56)	0.93 (0.35,2.48)	I	1.32 (0.45,3.88)
A	3.08 (0.60,15.75)	2.51 (0.64,9.81)	2.20 (0.55,8.70)	1.93 (0.30,12.21)	1.62 (0.79,3.31)	1.56 (0.42,5.78)	1.37 (0.39,4.78)	1.28 (0.37,4.39)	0.76 (0.26,2.24)	A

Abbreviation: A = BortPred, B = BortThal, C = Daratumumab, D = IFN, E = Ixazomib, F = Len, G = LenPred, H = Placebo, I = Thal, J = ThalIFN.

BortThal: bortezomib-thalidomide; IFN: interferon; LenPred: lenalidomide- prednisone; Thal: thalidomide; ThalIFN: thalidomide- interferon.

Table 7. Matrix of pairwise comparisons of regimens on 36 months OS rate (shown as odds ratios and 95% confidence intervals).

	C	E	B	F	G	A	H	D	I
SUCRA (%)	87.1	81.6	67.5	54.2	43.6	41.6	28.2	25.7	20.4
C	C	0.91 (0.58,1.44)	0.74 (0.27,2.03)	0.64 (0.26,1.59)	0.55 (0.39,0.77)	0.53 (0.16,1.75)	0.47 (0.30,0.73)	0.42 (0.16,1.05)	0.36 (0.11,1.17)
E	1.10 (0.69,1.74)	E	0.81 (0.30,2.20)	0.70 (0.32,1.54)	0.60 (0.44,0.82)	0.58 (0.18,1.91)	0.51 (0.33,0.79)	0.46 (0.18,1.14)	0.40 (0.13,1.27)
B	1.36 (0.49,3.73)	1.24 (0.45,3.37)	B	0.87 (0.24,3.10)	0.74 (0.29,1.92)	0.72 (0.38,1.37)	0.63 (0.26,1.57)	0.56 (0.23,1.36)	0.49 (0.16,1.53)
F	1.56 (0.63,3.88)	1.42 (0.65,3.12)	1.15 (0.32,4.11)	F	0.85 (0.37,1.98)	0.82 (0.20,3.43)	0.73 (0.30,1.78)	0.65 (0.19,2.16)	0.57 (0.14,2.30)
G	1.83 (1.31,2.58)	1.67 (1.23,2.28)	1.35 (0.52,3.50)	1.17 (0.51,2.72)	G	0.97 (0.31,3.06)	0.86 (0.64,1.15)	0.76 (0.32,1.80)	0.67 (0.22,2.04)
A	1.89 (0.57,6.29)	1.73 (0.52,5.68)	1.40 (0.73,2.66)	1.21 (0.29,5.04)	1.03 (0.33,3.26)	A	0.91 (0.37,2.21)	0.79 (0.26,2.35)	0.88 (0.29,2.69)
H	2.14 (1.36,3.37)	1.95 (1.27,3.00)	1.58 (0.64,3.91)	1.37 (0.56,3.35)	1.17 (0.87,1.57)	1.10 (0.45,2.69)	H	0.89 (0.40,2.00)	0.78 (0.27,2.29)
D	2.41 (0.95,6.08)	2.20 (0.88,5.48)	1.77 (0.73,4.29)	1.54 (0.46,5.14)	1.31 (0.56,3.11)	1.27 (0.43,3.79)	1.12 (0.50,2.52)	D	0.88 (0.43,1.78)
I	2.75 (0.86,8.82)	2.50 (0.79,7.97)	2.02 (0.65,6.29)	1.76 (0.43,7.11)	1.50 (0.49,4.57)	1.13 (0.37,3.44)	1.28 (0.44,3.76)	1.14 (0.56,2.32)	I

Abbreviation: A = BortPred, B = BortThal, C = Daratumumab, D = IFN, E = Len, F = LenPred, G = Placebo, H = Thal, I = ThalIFN.

BortThal: bortezomib-thalidomide; IFN: interferon; LenPred: lenalidomide- prednisone; Thal: thalidomide; ThalIFN: thalidomide- interferon.

Table 8. Matrix of pairwise comparisons of regimens on 42 months OS rate (shown as odds ratios and 95% confidence intervals).

	C	E	B	A	F	G	H	D	I
SUCRA (%)	90.8	77.7	75.1	52.8	40	39.5	30.3	28.2	15.6
C	C	0.81 (0.52,1.25)	0.78 (0.31,1.96)	0.59 (0.19,1.81)	0.49 (0.21,1.15)	0.48 (0.35,0.67)	0.45 (0.29,0.69)	0.41 (0.18,0.96)	0.32 (0.11,0.95)
E	1.24 (0.80,1.91)	E	0.96 (0.38,2.40)	0.73 (0.24,2.23)	0.60 (0.29,1.27)	0.60 (0.45,0.80)	0.55 (0.37,0.83)	0.51 (0.22,1.17)	0.39 (0.13,1.17)
B	1.29 (0.51,3.27)	1.04 (0.42,2.61)	B	0.76 (0.40,1.43)	0.63 (0.19,2.05)	0.62 (0.26,1.49)	0.57 (0.25,1.31)	0.53 (0.24,1.18)	0.41 (0.14,1.19)
A	1.70 (0.55,5.23)	1.37 (0.45,4.18)	1.32 (0.70,2.48)	A	0.83 (0.22,3.16)	0.82 (0.28,2.41)	1.07 (0.47,2.42)	0.70 (0.25,1.94)	0.76 (0.27,2.14)
F	2.05 (0.87,4.85)	1.66 (0.79,3.48)	1.59 (0.49,5.18)	1.21 (0.32,4.62)	F	0.99 (0.45,2.20)	0.91 (0.39,2.13)	0.84 (0.27,2.57)	0.65 (0.17,2.44)
G	2.07 (1.50,2.86)	1.67 (1.25,2.23)	1.60 (0.67,3.83)	1.22 (0.41,3.58)	1.01 (0.45,2.24)	G	0.92 (0.69,1.23)	0.85 (0.39,1.86)	0.66 (0.23,1.88)
H	2.25 (1.46,3.46)	1.81 (1.21,2.72)	1.74 (0.76,3.97)	0.93 (0.41,2.11)	1.09 (0.47,2.55)	1.09 (0.82,1.45)	H	0.92 (0.44,1.91)	0.71 (0.26,1.96)
D	2.44 (1.04,5.71)	1.97 (0.85,4.55)	1.89 (0.84,4.24)	1.44 (0.52,4.02)	1.19 (0.39,3.64)	1.18 (0.54,2.59)	1.09 (0.52,2.26)	D	0.78 (0.39,1.56)
I	3.15 (1.05,9.46)	2.54 (0.85,7.57)	2.44 (0.84,7.11)	1.32 (0.47,3.74)	1.53 (0.41,5.74)	1.52 (0.53,4.36)	1.40 (0.51,3.86)	1.29 (0.64,2.60)	I

Abbreviation: A = BortPred, B = BortThal, C = Daratumumab, D = IFN, E = Len, F = LenPred, G = Placebo, H = Thal, I = ThalIFN.

BortThal: bortezomib-thalidomide; IFN: interferon; LenPred: lenalidomide- prednisone; Thal: thalidomide; ThalIFN: thalidomide- interferon.

Table 9. Matrix of pairwise comparisons of regimens on 48 months OS rate (shown as odds ratios and 95% confidence intervals).

	C	E	B	G	A	H	F	D	I
SUCRA (%)	96.1	78.1	77.7	43.7	37.2	30.5	30.2	29.2	27.3
C	C	0.68 (0.43,1.10)	0.67 (0.29,1.59)	0.41 (0.30,0.57)	0.39 (0.13,1.11)	0.37 (0.24,0.56)	0.35 (0.15,0.81)	0.35 (0.16,0.77)	0.33 (0.11,0.93)
E	1.46 (0.91,2.35)	E	0.99 (0.41,2.36)	0.61 (0.43,0.86)	0.56 (0.19,1.64)	0.54 (0.34,0.84)	0.51 (0.25,1.03)	0.51 (0.23,1.14)	0.48 (0.16,1.38)
B	1.48 (0.63,3.50)	1.01 (0.42,2.42)	B	0.61 (0.28,1.36)	0.57 (0.31,1.06)	0.55 (0.26,1.15)	0.51 (0.17,1.58)	0.52 (0.25,1.07)	0.48 (0.18,1.33)
G	2.41 (1.76,3.31)	1.65 (1.16,2.35)	1.63 (0.73,3.61)	G	0.93 (0.34,2.55)	0.89 (0.67,1.17)	0.84 (0.38,1.84)	0.84 (0.41,1.73)	0.79 (0.29,2.15)
A	2.59 (0.90,7.44)	1.77 (0.61,5.14)	1.74 (0.94,3.23)	1.07 (0.39,2.93)	A	1.18 (0.56,2.53)	0.90 (0.25,3.23)	0.90 (0.34,2.34)	0.95 (0.36,2.50)
H	2.72 (1.79,4.15)	1.86 (1.19,2.91)	1.83 (0.87,3.87)	1.13 (0.85,1.49)	0.84 (0.40,1.80)	H	0.94 (0.41,2.18)	0.94 (0.48,1.85)	0.89 (0.34,2.33)
F	2.88 (1.23,6.76)	1.97 (0.97,4.00)	1.94 (0.63,5.97)	1.19 (0.54,2.63)	1.11 (0.31,4.00)	1.06 (0.46,2.45)	F	1.00 (0.34,2.93)	0.94 (0.26,3.38)
D	2.88 (1.31,6.36)	1.97 (0.88,4.41)	1.94 (0.93,4.05)	1.19 (0.58,2.47)	1.11 (0.43,2.90)	1.06 (0.54,2.07)	1.00 (0.34,2.92)	D	0.94 (0.47,1.88)
I	3.07 (1.07,8.80)	2.10 (0.72,6.08)	2.07 (0.75,5.69)	1.27 (0.47,3.47)	1.05 (0.40,2.76)	1.13 (0.43,2.96)	1.06 (0.30,3.82)	1.06 (0.53,2.13)	I

Abbreviation: A = BortPred, B = BortThal, C = Daratumumab, D = IFN, E = Len, F = LenPred, G = Placebo, H = Thal, I = ThalIFN.

BortThal: bortezomib-thalidomide; IFN: interferon; LenPred: lenalidomide- prednisone; Thal: thalidomide; ThalIFN: thalidomide- interferon.

Table 10. Matrix of pairwise comparisons of regimens on 6 months PFS rate (shown as odds ratios and 95% confidence intervals).

	C	K	E	B	A	G	F	J	H	I	E
SUCRA (%)	83.8	74	74.2	71.6	58.6	46.9	44	38.5	33.3	16.1	11.2
C	C	0.80 (0.14,4.59)	0.75 (0.13,4.23)	0.63 (0.19,2.07)	0.61 (0.08,4.78)	0.44 (0.15,1.29)	0.43 (0.13,1.35)	0.40 (0.12,1.30)	0.37 (0.10,1.30)	0.31 (0.10,0.97)	0.23 (0.05,1.07)
K	1.26 (0.22,7.23)	K	0.94 (0.22,3.99)	0.79 (0.19,3.18)	1.52 (0.28,8.27)	0.55 (0.14,2.19)	0.53 (0.14,2.09)	0.50 (0.14,1.83)	0.46 (0.10,2.13)	0.39 (0.10,1.50)	0.29 (0.12,0.67)
B	1.33 (0.24,7.51)	1.06 (0.25,4.49)	B	0.83 (0.21,3.28)	0.81 (0.26,2.50)	0.58 (0.15,2.26)	0.57 (0.15,2.16)	0.53 (0.15,1.89)	0.49 (0.11,2.21)	0.42 (0.11,1.55)	0.31 (0.10,0.99)
D	1.60 (0.48,5.29)	1.27 (0.31,5.15)	1.20 (0.30,4.73)	D	0.97 (0.16,5.73)	0.70 (0.42,1.18)	0.68 (0.42,1.10)	0.64 (0.38,1.09)	0.59 (0.25,1.37)	0.50 (0.34,0.75)	0.37 (0.12,1.12)
A	1.65 (0.21,13.05)	0.66 (0.12,3.60)	1.24 (0.40,3.85)	1.03 (0.17,6.11)	A	0.72 (0.12,4.23)	0.70 (0.12,4.05)	0.79 (0.26,2.42)	0.61 (0.09,4.00)	0.52 (0.09,2.92)	0.38 (0.07,1.94)
G	2.28 (0.78,6.70)	1.82 (0.46,7.21)	1.71 (0.44,6.62)	1.43 (0.85,2.40)	1.38 (0.24,8.04)	G	0.97 (0.64,1.48)	0.91 (0.56,1.47)	0.84 (0.43,1.63)	0.71 (0.51,0.99)	0.52 (0.18,1.56)
F	2.35 (0.74,7.48)	1.87 (0.48,7.33)	1.76 (0.46,6.72)	1.47 (0.91,2.37)	1.42 (0.25,8.20)	1.03 (0.68,1.57)	F	0.94 (0.61,1.45)	0.87 (0.39,1.90)	0.74 (0.57,0.96)	0.54 (0.18,1.58)
J	2.50 (0.77,8.15)	1.99 (0.55,7.27)	1.88 (0.53,6.66)	1.57 (0.92,2.66)	1.27 (0.41,3.92)	1.10 (0.68,1.77)	1.07 (0.69,1.65)	J	0.92 (0.41,2.09)	0.78 (0.55,1.11)	0.58 (0.22,1.54)
H	2.72 (0.77,9.62)	2.16 (0.47,9.98)	2.04 (0.45,9.19)	1.70 (0.73,3.94)	1.64 (0.25,10.81)	1.19 (0.62,2.31)	1.16 (0.53,2.53)	1.08 (0.48,2.45)	H	0.85 (0.41,1.78)	0.62 (0.17,2.24)
I	3.19 (1.03,9.86)	2.54 (0.67,9.70)	2.40 (0.65,8.89)	2.00 (1.34,2.98)	1.93 (0.34,10.92)	1.40 (1.01,1.95)	1.36 (1.04,1.77)	1.28 (0.90,1.80)	1.18 (0.56,2.46)	I	0.73 (0.26,2.08)
E	4.35 (0.94,20.17)	3.46 (1.49,8.03)	3.26 (1.01,10.52)	2.72 (0.89,8.30)	2.63 (0.52,13.41)	1.91 (0.64,5.69)	1.85 (0.63,5.41)	1.74 (0.65,4.63)	1.60 (0.45,5.74)	1.36 (0.48,3.86)	E

Abbreviation: A = BortPred, B = BortThal, C = CarfilzomibLen, D = Daratumumab, E = IFN, F = Ixazomib, G = Len, H = LenPred, I = Placebo, J = Thal, K = ThalIFN.

CarfilzomibLen: Carfilzomib-lenalidomide; BortThal: bortezomib-thalidomide; IFN: interferon; LenPred: lenalidomide- prednisone; Thal: thalidomide; ThalIFN: thalidomide- interferon.

Table 11. Matrix of pairwise comparisons of regimens on 12 months PFS rate (shown as odds ratios and 95% confidence intervals).

	C	H	G	B	D	K	F	J	A	I	E
SUCRA (%)	90.3	84.4	68.6	65	60.5	48.1	45.6	35.9	25.7	18.3	7.6
C	C	0.81 (0.34,1.92)	0.62 (0.30,1.29)	0.59 (0.16,2.11)	0.55 (0.23,1.32)	0.45 (0.11,1.90)	0.46 (0.20,1.07)	0.39 (0.16,0.97)	0.30 (0.07,1.34)	0.31 (0.14,0.67)	0.22 (0.06,0.72)
H	1.24 (0.52,2.93)	H	0.76 (0.49,1.20)	0.73 (0.23,2.27)	0.68 (0.36,1.31)	0.55 (0.15,2.08)	0.57 (0.31,1.05)	0.49 (0.25,0.97)	0.37 (0.09,1.47)	0.38 (0.23,0.64)	0.27 (0.09,0.77)
G	1.62 (0.78,3.39)	1.31 (0.84,2.05)	G	0.95 (0.33,2.71)	0.89 (0.56,1.42)	0.73 (0.21,2.52)	0.74 (0.49,1.13)	0.64 (0.38,1.07)	0.49 (0.13,1.79)	0.50 (0.39,0.65)	0.35 (0.14,0.91)
B	1.70 (0.47,6.11)	1.37 (0.44,4.29)	1.05 (0.37,2.99)	B	0.94 (0.32,2.78)	0.76 (0.24,2.45)	0.78 (0.27,2.25)	0.67 (0.27,1.66)	0.51 (0.23,1.11)	0.52 (0.19,1.45)	0.37 (0.16,0.87)
D	1.81 (0.76,4.33)	1.46 (0.77,2.80)	1.12 (0.70,1.78)	1.06 (0.36,3.15)	D	0.81 (0.23,2.91)	0.83 (0.50,1.37)	0.71 (0.39,1.29)	0.54 (0.14,2.06)	0.56 (0.38,0.82)	0.39 (0.15,1.06)
K	2.23 (0.53,9.48)	1.81 (0.48,6.78)	1.38 (0.40,4.78)	1.31 (0.41,4.23)	1.23 (0.34,4.42)	K	1.02 (0.29,3.60)	0.88 (0.28,2.72)	0.76 (0.23,2.52)	0.69 (0.20,2.33)	0.48 (0.22,1.08)
F	2.19 (0.94,5.11)	1.77 (0.96,3.27)	1.35 (0.89,2.05)	1.29 (0.44,3.73)	1.21 (0.73,2.00)	0.98 (0.28,3.45)	F	0.86 (0.49,1.50)	0.66 (0.18,2.45)	0.68 (0.49,0.94)	0.47 (0.18,1.25)
J	2.54 (1.03,6.26)	2.05 (1.03,4.08)	1.57 (0.94,2.63)	1.49 (0.60,3.71)	1.40 (0.78,2.54)	1.14 (0.37,3.53)	1.16 (0.67,2.02)	J	1.20 (0.46,3.15)	0.78 (0.50,1.23)	0.55 (0.25,1.23)
A	3.33 (0.75,14.88)	2.69 (0.68,10.68)	2.06 (0.56,7.56)	1.96 (0.90,4.26)	1.84 (0.48,6.98)	1.31 (0.40,4.33)	1.52 (0.41,5.68)	0.83 (0.32,2.18)	A	1.03 (0.29,3.69)	0.72 (0.23,2.29)
I	3.24 (1.48,7.08)	2.62 (1.56,4.40)	2.00 (1.54,2.59)	1.91 (0.69,5.25)	1.79 (1.22,2.63)	1.45 (0.43,4.90)	1.48 (1.07,2.05)	1.27 (0.81,2.00)	0.97 (0.27,3.49)	I	0.70 (0.28,1.76)
E	4.62 (1.38,15.40)	3.73 (1.30,10.70)	2.85 (1.10,7.39)	2.71 (1.16,6.37)	2.55 (0.94,6.90)	2.07 (0.93,4.60)	2.11 (0.80,5.58)	1.82 (0.82,4.04)	1.39 (0.44,4.40)	1.42 (0.57,3.56)	E

Abbreviation: A = BortPred, B = BortThal, C = CarfilzomiLen, D = Daratumumab, E = IFN, F = Ixazomib, G = Len, H = LenPred, I = Placebo, J = Thal, K = ThalIFN.

CarfilzomibLen: Carfilzomib-lenalidomide; BortThal: bortezomib-thalidomide; IFN: interferon; LenPred: lenalidomide- prednisone; Thal: thalidomide; ThalIFN: thalidomide- interferon.

Table 12. Matrix of pairwise comparisons of regimens on 18 months PFS rate (shown as odds ratios and 95% confidence intervals).

	C	H	G	B	F	D	K	J	A	I	E
SUCRA (%)	98.2	85.4	74	68	47.5	50	40.3	34.2	31	11.1	10.2
C	C	0.58 (0.27,1.25)	0.46 (0.23,0.88)	0.41 (0.13,1.25)	0.30 (0.14,0.64)	0.31 (0.15,0.67)	0.26 (0.07,0.95)	0.25 (0.11,0.55)	0.22 (0.06,0.82)	0.17 (0.08,0.33)	0.16 (0.05,0.45)
H	1.73 (0.80,3.74)	H	0.79 (0.53,1.17)	0.71 (0.27,1.89)	0.52 (0.30,0.89)	0.54 (0.31,0.94)	0.45 (0.14,1.47)	0.43 (0.23,0.78)	0.39 (0.12,1.27)	0.29 (0.18,0.45)	0.27 (0.11,0.68)
G	2.20 (1.13,4.26)	1.27 (0.86,1.89)	G	0.90 (0.37,2.21)	0.66 (0.46,0.95)	0.69 (0.47,1.01)	0.57 (0.18,1.75)	0.54 (0.34,0.85)	0.49 (0.16,1.51)	0.36 (0.29,0.45)	0.34 (0.15,0.79)
B	2.44 (0.80,7.44)	1.41 (0.53,3.76)	1.11 (0.45,2.72)	B	0.74 (0.29,1.84)	0.76 (0.30,1.92)	0.63 (0.22,1.82)	0.60 (0.28,1.31)	0.54 (0.28,1.07)	0.40 (0.17,0.96)	0.38 (0.18,0.80)
F	3.31 (1.56,7.05)	1.92 (1.12,3.28)	1.51 (1.05,2.17)	1.36 (0.54,3.39)	F	1.04 (0.68,1.59)	0.86 (0.27,2.68)	0.82 (0.50,1.34)	0.74 (0.24,2.31)	0.55 (0.41,0.73)	0.52 (0.22,1.22)
D	3.20 (1.49,6.87)	1.85 (1.07,3.21)	1.46 (0.99,2.14)	1.31 (0.52,3.30)	0.96 (0.63,1.48)	D	0.83 (0.26,2.60)	0.79 (0.48,1.31)	0.71 (0.23,2.24)	0.53 (0.39,0.72)	0.50 (0.21,1.18)
K	3.87 (1.05,14.26)	2.24 (0.68,7.36)	1.76 (0.57,5.42)	1.59 (0.55,4.57)	1.17 (0.37,3.65)	1.21 (0.38,3.81)	K	0.96 (0.34,2.67)	0.90 (0.32,2.53)	0.64 (0.21,1.92)	0.60 (0.28,1.29)
J	4.05 (1.81,9.03)	2.34 (1.28,4.27)	1.84 (1.17,2.90)	1.66 (0.77,3.59)	1.22 (0.75,2.00)	1.27 (0.76,2.10)	1.05 (0.37,2.93)	J	0.82 (0.36,1.90)	0.67 (0.45,0.99)	0.63 (0.31,1.27)
A	4.49 (1.22,16.54)	2.59 (0.79,8.54)	2.04 (0.66,6.29)	1.84 (0.93,3.63)	1.35 (0.43,4.24)	1.40 (0.45,4.42)	1.11 (0.40,3.10)	1.22 (0.53,2.81)	A	0.74 (0.25,2.23)	0.70 (0.26,1.92)
I	6.05 (3.01,12.16)	3.50 (2.23,5.50)	2.76 (2.21,3.44)	2.48 (1.04,5.91)	1.83 (1.36,2.45)	1.89 (1.38,2.60)	1.56 (0.52,4.71)	1.50 (1.01,2.22)	1.35 (0.45,4.07)	I	0.95 (0.42,2.11)
E	6.40 (2.21,18.54)	3.70 (1.47,9.30)	2.91 (1.27,6.70)	2.62 (1.25,5.52)	1.93 (0.82,4.54)	2.00 (0.84,4.75)	1.65 (0.78,3.52)	1.58 (0.79,3.18)	1.43 (0.52,3.91)	1.06 (0.47,2.36)	E

Abbreviation: A = BortPred, B = BortThal, C = CarfilzomiLen, D = Daratumumab, E = IFN, F = Ixazomib, G = Len, H = LenPred, I = Placebo, J = Thal, K = ThalIFN.

CarfilzomibLen: Carfilzomib-lenalidomide; BortThal: bortezomib-thalidomide; IFN: interferon; LenPred: lenalidomide- prednisone; Thal: thalidomide; ThalIFN: thalidomide- interferon.

Table 13. Matrix of pairwise comparisons of regimens on 24 months PFS rate (shown as odds ratios and 95% confidence intervals).

	C	H	B	G	A	D	K	J	F	E	I
SUCRA (%)	95.8	82.7	76.1	63.6	56	50.4	45.6	33.5	31.1	10.2	5
C	C	0.65 (0.32,1.33)	0.57 (0.20,1.67)	0.45 (0.25,0.83)	0.42 (0.12,1.48)	0.38 (0.18,0.77)	0.34 (0.09,1.23)	0.29 (0.14,0.63)	0.28 (0.14,0.58)	0.18 (0.06,0.50)	0.16 (0.08,0.30)
H	1.54 (0.75,3.17)	H	0.88 (0.34,2.32)	0.70 (0.47,1.03)	0.65 (0.20,2.10)	0.58 (0.33,1.00)	0.53 (0.16,1.74)	0.45 (0.24,0.84)	0.44 (0.25,0.75)	0.28 (0.11,0.70)	0.24 (0.15,0.38)
B	1.74 (0.60,5.06)	1.13 (0.43,2.96)	B	0.79 (0.33,1.90)	0.73 (0.38,1.43)	0.65 (0.26,1.62)	0.59 (0.21,1.71)	0.51 (0.24,1.07)	0.49 (0.20,1.22)	0.31 (0.15,0.65)	0.27 (0.12,0.64)
G	2.21 (1.21,4.04)	1.43 (0.97,2.13)	1.27 (0.53,3.06)	G	0.93 (0.31,2.81)	0.83 (0.56,1.22)	0.75 (0.24,2.34)	0.65 (0.40,1.04)	0.63 (0.43,0.91)	0.40 (0.17,0.91)	0.35 (0.28,0.44)
A	2.37 (0.67,8.36)	1.54 (0.48,4.98)	1.36 (0.70,2.66)	1.07 (0.36,3.24)	A	0.89 (0.29,2.75)	0.70 (0.26,1.89)	1.14 (0.50,2.60)	0.67 (0.22,2.07)	0.43 (0.16,1.15)	0.37 (0.13,0.99)
D	2.66 (1.30,5.45)	1.73 (1.00,3.00)	1.53 (0.62,3.79)	1.20 (0.82,1.77)	1.12 (0.36,3.46)	D	0.91 (0.29,2.88)	0.78 (0.46,1.32)	0.75 (0.49,1.17)	0.48 (0.20,1.13)	0.42 (0.31,0.58)
K	2.93 (0.81,10.58)	1.90 (0.57,6.31)	1.68 (0.59,4.84)	1.33 (0.43,4.12)	1.44 (0.53,3.90)	1.10 (0.35,3.49)	K	0.86 (0.31,2.40)	0.83 (0.26,2.63)	0.53 (0.24,1.14)	0.46 (0.15,1.40)
J	3.41 (1.58,7.36)	2.21 (1.19,4.11)	1.96 (0.94,4.11)	1.54 (0.96,2.48)	0.88 (0.39,2.00)	1.28 (0.76,2.17)	1.16 (0.42,3.25)	J	0.97 (0.57,1.62)	0.62 (0.31,1.21)	0.54 (0.35,0.82)
F	3.53 (1.73,7.20)	2.29 (1.33,3.96)	2.03 (0.82,5.01)	1.60 (1.10,2.33)	1.49 (0.48,4.58)	1.33 (0.85,2.06)	1.20 (0.38,3.81)	1.04 (0.62,1.74)	F	0.64 (0.27,1.50)	0.56 (0.41,0.76)
E	5.54 (1.99,15.45)	3.60 (1.44,9.00)	3.18 (1.55,6.55)	2.51 (1.09,5.74)	2.33 (0.87,6.24)	2.08 (0.88,4.91)	1.89 (0.87,4.08)	1.62 (0.82,3.20)	1.57 (0.67,3.69)	E	0.87 (0.39,1.94)
I	6.34 (3.33,12.07)	4.12 (2.62,6.47)	3.64 (1.56,8.53)	2.87 (2.30,3.58)	2.67 (1.01,7.88)	2.38 (1.74,3.27)	2.16 (0.71,6.56)	1.86 (1.22,2.83)	1.80 (1.32,2.44)	1.14 (0.52,2.54)	I

Abbreviation: A = BortPred, B = BortThal, C = CarfilzomiLen, D = Daratumumab, E = IFN, F = Ixazomib, G = Len, H = LenPred, I = Placebo, J = Thal, K = ThalIFN.

CarfilzomibLen: Carfilzomib-lenalidomide; BortThal: bortezomib-thalidomide; IFN: interferon; LenPred: lenalidomide- prednisone; Thal: thalidomide; ThalIFN: thalidomide- interferon.

Table 14. Matrix of pairwise comparisons of regimens on 30 months PFS rate (shown as odds ratios and 95% confidence intervals).

	C	H	B	G	D	K	A	F	J	E	I
SUCRA (%)	96	83.5	66.5	65.9	60.4	50.3	44.3	36.3	26.9	13.8	6
C	C	0.64 (0.28,1.44)	0.45 (0.14,1.48)	0.46 (0.23,0.90)	0.42 (0.18,0.96)	0.34 (0.08,1.46)	0.31 (0.08,1.27)	0.28 (0.12,0.64)	0.23 (0.09,0.57)	0.17 (0.05,0.57)	0.14 (0.07,0.30)
H	1.56 (0.69,3.53)	H	0.70 (0.23,2.09)	0.72 (0.45,1.14)	0.65 (0.34,1.27)	0.53 (0.14,2.09)	0.49 (0.13,1.82)	0.44 (0.23,0.85)	0.36 (0.17,0.78)	0.27 (0.09,0.80)	0.22 (0.13,0.38)
B	2.23 (0.67,7.40)	1.43 (0.48,4.26)	B	1.03 (0.38,2.76)	0.93 (0.33,2.62)	0.76 (0.24,2.40)	0.69 (0.33,1.47)	0.63 (0.22,1.75)	0.52 (0.24,1.13)	0.39 (0.18,0.85)	0.32 (0.12,0.83)
G	2.18 (1.11,4.27)	1.39 (0.88,2.21)	0.98 (0.36,2.63)	G	0.91 (0.56,1.47)	0.74 (0.20,2.69)	0.68 (0.20,2.34)	0.61 (0.38,0.98)	0.50 (0.27,0.93)	0.38 (0.15,1.00)	0.31 (0.24,0.41)
D	2.39 (1.05,5.47)	1.53 (0.79,2.97)	1.07 (0.38,3.00)	1.10 (0.68,1.77)	D	0.81 (0.22,3.04)	0.74 (0.21,2.65)	0.67 (0.39,1.16)	0.55 (0.28,1.08)	0.42 (0.15,1.14)	0.34 (0.23,0.51)
K	2.94 (0.69,12.62)	1.88 (0.48,7.41)	1.32 (0.42,4.18)	1.35 (0.37,4.91)	1.23 (0.33,4.61)	K	1.34 (0.45,3.95)	0.83 (0.22,3.09)	0.68 (0.22,2.13)	0.52 (0.22,1.21)	0.42 (0.12,1.49)
A	3.22 (0.79,13.24)	2.06 (0.55,7.75)	1.44 (0.68,3.05)	1.48 (0.43,5.13)	1.35 (0.38,4.82)	0.75 (0.25,2.20)	A	0.90 (0.25,3.22)	1.74 (0.68,4.48)	0.56 (0.19,1.65)	0.46 (0.14,1.56)
F	3.57 (1.57,8.13)	2.28 (1.18,4.42)	1.60 (0.57,4.47)	1.64 (1.02,2.63)	1.49 (0.86,2.59)	1.21 (0.32,4.53)	1.11 (0.31,3.95)	F	0.83 (0.42,1.61)	0.62 (0.23,1.70)	0.51 (0.35,0.76)
J	4.32 (1.74,10.71)	2.76 (1.29,5.93)	1.93 (0.89,4.22)	1.98 (1.08,3.65)	1.81 (0.92,3.53)	1.47 (0.47,4.57)	0.57 (0.22,1.48)	1.21 (0.62,2.36)	J	0.76 (0.36,1.60)	0.62 (0.36,1.07)
E	5.72 (1.76,18.55)	3.65 (1.25,10.65)	2.56 (1.18,5.54)	2.62 (1.00,6.89)	2.39 (0.87,6.53)	1.94 (0.82,4.57)	1.77 (0.60,5.20)	1.60 (0.59,4.37)	1.32 (0.63,2.80)	E	0.82 (0.33,2.07)
I	6.95 (3.36,14.38)	4.44 (2.60,7.59)	3.11 (1.20,8.06)	3.19 (2.42,4.20)	2.91 (1.96,4.31)	2.36 (0.67,8.33)	2.16 (0.64,7.24)	1.95 (1.32,2.87)	1.61 (0.93,2.78)	1.22 (0.48,3.07)	I

Abbreviation: A = BortPred, B = BortThal, C = CarfilzomiLen, D = Daratumumab, E = IFN, F = Ixazomib, G = Len, H = LenPred, I = Placebo, J = Thal, K = ThalIFN.

CarfilzomibLen: Carfilzomib-lenalidomide; BortThal: bortezomib-thalidomide; IFN: interferon; LenPred: lenalidomide- prednisone; Thal: thalidomide; ThalIFN: thalidomide- interferon.

Table 15. Matrix of pairwise comparisons of regimens on 36 months PFS rate (shown as odds ratios and 95% confidence intervals).

	C	H	G	B	D	K	A	F	J	E	I
SUCRA (%)	90.9	72.3	68.9	64.4	61.9	49.2	46	37.5	33	19.8	5.9
C	C	0.64 (0.25,1.62)	0.60 (0.28,1.27)	0.53 (0.14,2.11)	0.53 (0.20,1.40)	0.41 (0.08,2.19)	0.40 (0.08,2.00)	0.36 (0.14,0.96)	0.33 (0.11,0.97)	0.25 (0.06,0.99)	0.18 (0.08,0.42)
H	1.56 (0.62,3.95)	H	0.93 (0.55,1.59)	0.84 (0.24,2.95)	0.84 (0.37,1.86)	0.65 (0.13,3.13)	0.63 (0.14,2.86)	0.57 (0.25,1.28)	0.52 (0.20,1.32)	0.40 (0.11,1.39)	0.28 (0.15,0.54)
G	1.68 (0.79,3.58)	1.07 (0.63,1.83)	G	0.90 (0.29,2.81)	0.90 (0.49,1.63)	0.70 (0.16,3.06)	0.67 (0.16,2.78)	0.61 (0.33,1.13)	0.56 (0.26,1.19)	0.42 (0.14,1.32)	0.30 (0.21,0.43)
B	1.87 (0.47,7.37)	1.20 (0.34,4.23)	1.11 (0.36,3.50)	B	1.00 (0.31,3.27)	0.78 (0.22,2.77)	0.75 (0.32,1.74)	0.68 (0.21,2.24)	0.62 (0.26,1.45)	0.47 (0.20,1.10)	0.34 (0.11,0.99)
D	1.87 (0.71,4.90)	1.20 (0.54,2.67)	1.11 (0.61,2.03)	1.00 (0.31,3.27)	D	0.78 (0.17,3.53)	0.75 (0.17,3.21)	0.68 (0.34,1.35)	0.62 (0.27,1.42)	0.47 (0.15,1.54)	0.34 (0.21,0.54)
K	2.41 (0.46,12.73)	1.54 (0.32,7.45)	1.44 (0.33,6.32)	1.29 (0.36,4.61)	1.29 (0.28,5.86)	K	1.21 (0.36,4.00)	0.88 (0.19,4.01)	0.80 (0.22,2.84)	0.61 (0.24,1.58)	0.43 (0.10,1.82)
A	2.50 (0.50,12.51)	1.60 (0.35,7.30)	1.49 (0.36,6.17)	1.34 (0.57,3.11)	1.34 (0.31,5.73)	0.83 (0.25,2.75)	A	0.91 (0.21,3.92)	1.58 (0.53,4.70)	0.63 (0.19,2.09)	0.45 (0.11,1.78)
F	2.75 (1.04,7.27)	1.76 (0.78,3.96)	1.64 (0.89,3.02)	1.47 (0.45,4.84)	1.47 (0.74,2.92)	1.14 (0.25,5.21)	1.10 (0.25,4.74)	F	0.91 (0.39,2.10)	0.70 (0.21,2.27)	0.49 (0.30,0.81)
J	3.02 (1.03,8.85)	1.93 (0.76,4.91)	1.80 (0.84,3.86)	1.61 (0.69,3.77)	1.61 (0.71,3.68)	1.25 (0.35,4.45)	0.63 (0.21,1.88)	1.10 (0.48,2.54)	J	0.76 (0.33,1.77)	0.54 (0.28,1.06)
E	3.95 (1.01,15.44)	2.53 (0.72,8.86)	2.35 (0.76,7.32)	2.11 (0.91,4.92)	2.11 (0.65,6.85)	1.64 (0.63,4.25)	1.58 (0.48,5.22)	1.44 (0.44,4.70)	1.31 (0.57,3.03)	E	0.71 (0.24,2.08)
I	5.57 (2.41,12.87)	3.56 (1.87,6.79)	3.32 (2.31,4.76)	2.98 (1.01,8.81)	2.98 (1.85,4.79)	2.31 (0.55,9.72)	2.23 (0.56,8.81)	2.03 (1.23,3.33)	1.85 (0.94,3.62)	1.41 (0.48,4.13)	I

Abbreviation: A = BortPred, B = BortThal, C = CarfilzomiLen, D = Daratumumab, E = IFN, F = Ixazomib, G = Len, H = LenPred, I = Placebo, J = Thal, K = ThalIFN.

CarfilzomibLen: Carfilzomib-lenalidomide; BortThal: bortezomib-thalidomide; IFN: interferon; LenPred: lenalidomide- prednisone; Thal: thalidomide; ThalIFN: thalidomide- interferon.

Table 16. Matrix of pairwise comparisons of regimens on 42 months PFS rate (shown as odds ratios and 95% confidence intervals).

	G	J	B	F	A	E	I	C	D	H
SUCRA (%)	76.6	75	68.9	65.9	53.5	43.1	42.9	37.8	30.4	5.9
G	G	1.08 (0.18,6.53)	0.87 (0.21,3.68)	0.81 (0.44,1.50)	0.70 (0.12,3.92)	0.57 (0.22,1.46)	0.57 (0.19,1.70)	0.51 (0.17,1.50)	0.46 (0.11,1.94)	0.28 (0.13,0.58)
J	0.92 (0.15,5.58)	J	0.81 (0.19,3.36)	0.75 (0.14,4.08)	1.22 (0.32,4.66)	0.52 (0.09,2.98)	0.53 (0.13,2.20)	0.47 (0.08,2.89)	0.42 (0.14,1.25)	0.26 (0.05,1.31)
B	1.15 (0.27,4.85)	1.24 (0.30,5.17)	B	0.93 (0.25,3.44)	0.80 (0.31,2.08)	0.65 (0.17,2.55)	0.65 (0.26,1.68)	0.59 (0.14,2.52)	0.53 (0.21,1.35)	0.32 (0.09,1.09)
F	1.23 (0.67,2.27)	1.33 (0.25,7.21)	1.07 (0.29,3.95)	F	0.86 (0.17,4.31)	0.70 (0.34,1.44)	0.70 (0.28,1.74)	0.63 (0.26,1.52)	0.56 (0.15,2.08)	0.34 (0.22,0.52)
A	1.43 (0.25,8.07)	0.82 (0.21,3.12)	1.25 (0.48,3.25)	1.17 (0.23,5.87)	A	0.81 (0.15,4.30)	2.21 (0.64,7.69)	0.73 (0.13,4.18)	0.66 (0.17,2.51)	0.40 (0.08,1.88)
E	1.76 (0.68,4.55)	1.91 (0.34,10.85)	1.54 (0.39,6.02)	1.43 (0.70,2.96)	1.23 (0.23,6.50)	E	1.01 (0.37,2.71)	0.90 (0.34,2.39)	0.81 (0.21,3.17)	0.49 (0.27,0.88)
I	1.75 (0.59,5.23)	1.89 (0.45,7.90)	1.53 (0.60,3.91)	1.42 (0.58,3.52)	0.45 (0.13,1.57)	0.99 (0.37,2.68)	I	0.89 (0.29,2.73)	0.80 (0.32,2.05)	0.48 (0.22,1.08)
C	1.96 (0.67,5.77)	2.12 (0.35,12.99)	1.71 (0.40,7.35)	1.59 (0.66,3.87)	1.37 (0.24,7.81)	1.11 (0.42,2.95)	1.12 (0.37,3.42)	C	0.90 (0.21,3.87)	0.54 (0.25,1.18)
D	2.18 (0.52,9.18)	2.35 (0.80,6.91)	1.90 (0.74,4.84)	1.77 (0.48,6.51)	1.52 (0.40,5.78)	1.23 (0.32,4.82)	1.24 (0.49,3.17)	1.11 (0.26,4.77)	D	0.60 (0.18,2.06)
H	3.62 (1.72,7.63)	3.91 (0.76,20.09)	3.15 (0.92,10.83)	2.94 (1.93,4.50)	2.52 (0.53,11.99)	2.05 (1.14,3.68)	2.07 (0.93,4.59)	1.85 (0.85,4.02)	1.66 (0.49,5.70)	H

Abbreviation: A = BortPred, B = BortThal, C = Daratumumab, D = IFN, E = Ixazomib, F = Len, G = LenPred, H = Placebo, I = Thal, J = ThalIFN.

BortThal: bortezomib-thalidomide; IFN: interferon; LenPred: lenalidomide- prednisone; Thal: thalidomide; ThalIFN: thalidomide- interferon.

Figure 3. A. Network plot of pairwise comparisons of regimens on 6,12,18 months OS. B. Network plot of pairwise comparisons of regimens on 24, 30 months OS. C. Network plot of pairwise comparisons of regimens on 36,42,48 months OS. D. Network plot of pairwise comparisons of regimens on 6, 12, 18, 24, 30, 36 months PFS. E. Network plot of pairwise comparisons of regimens on 42 months PFS. CarfilzomibLen: Carfilzomib-lenalidomide; BortThal: bortezomib-thalidomide; IFN: interferon; LenPred: lenalidomide- prednisone; Thal: thalidomide; ThalIFN: thalidomide- interferon.

Figure 4. The network funnel plots of pairwise comparisons of regimens on 6 months OS rate. Abbreviation: A = BortThal, B = Daratumumab, C = IFN, D = Ixazomib, E = Len, F = LenPred, G = Placebo, H = Thal, I = ThalIFN. The network funnel plots shows that there exist small sample effects in the studies of lenalidomide comparing placebo. BortThal: bortezomib-thalidomide; IFN: interferon; LenPred: lenalidomide- prednisone; Thal: thalidomide; ThalIFN: thalidomide- interferon.

Figure 5. The network funnel plots of pairwise comparisons of regimens on 12 months OS rate. Abbreviation: A = BortThal, B = Daratumumab, C = IFN, D = Ixazomib, E = Len, F = LenPred, G = Placebo, H = Thal, I = ThalIFN. The network funnel plots shows that there exist small sample effects in the studies of bortezomib-thalidomide comparing thalidomide. BortThal: bortezomib-thalidomide; IFN: interferon; LenPred: lenalidomide- prednisone; Thal: thalidomide; ThalIFN: thalidomide- interferon.

Figure 6. The network funnel plots of pairwise comparisons of regimens on 18 months OS rate. Abbreviation: A = BortThal, B = Daratumumab, C = IFN, D = Ixazomib, E = Len, F = LenPred, G = Placebo, H = Thal, I = ThalIFN. The network funnel plots shows that there exist small sample effects in the studies of lenalidomide comparing placebo. BortThal: bortezomib-thalidomide; IFN: interferon; LenPred: lenalidomide- prednisone; Thal: thalidomide; ThalIFN: thalidomide- interferon.

Figure 7. The network funnel plots of pairwise comparisons of regimens on 24 months OS rate. Abbreviation: A = BortPred, B = BortThal, C = Daratumumab, D = IFN, E = Ixazomib, F = Len, G = LenPred, H = Placebo, I = Thal, J = ThalIFN. The network funnel plots shows that there exist small sample effects in the studies of lenalidomide comparing placebo. BortThal: bortezomib-thalidomide; IFN: interferon; LenPred: lenalidomide- prednisone; Thal: thalidomide; ThalIFN: thalidomide- interferon.

Figure 8. The network funnel plots of pairwise comparisons of regimens on 30 months OS rate. Abbreviation: A = BortPred, B = BortThal, C = Daratumumab, D = IFN, E = Ixazomib, F = Len, G = LenPred, H = Placebo, I = Thal, J = ThalIFN. The network funnel plots shows that there exist small sample effects in the studies of ixazomib comparing placebo. BortThal: bortezomib-thalidomide; IFN: interferon; LenPred: lenalidomide- prednisone; Thal: thalidomide; ThalIFN: thalidomide- interferon.

Figure 9. The network funnel plots of pairwise comparisons of regimens on 36 months OS rate. Abbreviation: A = BortPred, B = BortThal, C = Daratumumab, D = IFN, E = Len, F = LenPred, G = Placebo, H = Thal, I = ThalIFN. The network funnel plots shows that there exist small sample effects in the studies of bortezomib-thalidomide comparing thalidomide. BortThal: bortezomib-thalidomide; IFN: interferon; LenPred: lenalidomide- prednisone; Thal: thalidomide; ThalIFN: thalidomide- interferon.

Figure 10. The network funnel plots of pairwise comparisons of regimens on 42 months OS rate. Abbreviation: A = BortPred, B = BortThal, C = Daratumumab, D = IFN, E = Len, F = LenPred, G = Placebo, H = Thal, I = ThalIFN. The network funnel plots shows that there exist small sample effects in the studies of bortezomib-thalidomide comparing thalidomide. BortThal: bortezomib-thalidomide; IFN: interferon; LenPred: lenalidomide- prednisone; Thal: thalidomide; ThalIFN: thalidomide- interferon.

Figure 11. The network funnel plots of pairwise comparisons of regimens on 48 months OS rate. Abbreviation: A = BortPred, B = BortThal, C = Daratumumab, D = IFN, E = Len, F = LenPred, G = Placebo, H = Thal, I = ThalIFN. The network funnel plots shows that there exist small sample effects in the studies of bortezomib-thalidomide comparing thalidomide. BortThal: bortezomib-thalidomide; IFN: interferon; LenPred: lenalidomide- prednisone; Thal: thalidomide; ThalIFN: thalidomide- interferon.

Figure 12. The network funnel plots of pairwise comparisons of regimens on 6 months PFS rate. Abbreviation: A = BortPred, B = BortThal, C = CarfilzomibLen, D = Daratumumab, E = IFN, F = Ixazomib, G = Len, H = LenPred, I = Placebo, J = Thal, K = ThalIFN. The network funnel plots shows that there exist small sample effects in the studies of lenalidomide comparing placebo. CarfilzomibLen: Carfilzomib-lenalidomide; BortThal: bortezomib-thalidomide; IFN: interferon; LenPred: lenalidomide- prednisone; Thal: thalidomide; ThalIFN: thalidomide- interferon.

Figure 13. The network funnel plots of pairwise comparisons of regimens on 12 months PFS rate. Abbreviation: A = BortPred, B = BortThal, C = CarfilzomiLen, D = Daratumumab, E = IFN, F = Ixazomib, G = Len, H = LenPred, I = Placebo, J = Thal, K = ThalIFN. The network funnel plots shows that there exist small sample effects in the studies of lenalidomide comparing placebo. CarfilzomibLen: Carfilzomib-lenalidomide; BortThal: bortezomib-thalidomide; IFN: interferon; LenPred: lenalidomide- prednisone; Thal: thalidomide; ThalIFN: thalidomide- interferon.

Figure 14. The network funnel plots of pairwise comparisons of regimens on 18 months PFS rate. Abbreviation: A = BortPred, B = BortThal, C = CarfilzomiLen, D = Daratumumab, E = IFN, F = Ixazomib, G = Len, H = LenPred, I = Placebo, J = Thal, K = ThalIFN. The network funnel plots shows that there exist small sample effects in the studies of lenalidomide comparing placebo. CarfilzomibLen: Carfilzomib-lenalidomide; BortThal: bortezomib-thalidomide; IFN: interferon; LenPred: lenalidomide- prednisone; Thal: thalidomide; ThalIFN: thalidomide- interferon.

Figure 15. The network funnel plots of pairwise comparisons of regimens on 24 months PFS rate. Abbreviation: A = BortPred, B = BortThal, C = CarfilzomiLen, D = Daratumumab, E = IFN, F = Ixazomib, G = Len, H = LenPred, I = Placebo, J = Thal, K = ThalIFN. The network funnel plots shows that there exist small sample effects in the studies of lenalidomide comparing placebo. CarfilzomibLen: Carfilzomib-lenalidomide; BortThal: bortezomib-thalidomide; IFN: interferon; LenPred: lenalidomide- prednisone; Thal: thalidomide; ThalIFN: thalidomide- interferon.

Figure 16. The network funnel plots of pairwise comparisons of regimens on 30 months PFS rate. Abbreviation: A = BortPred, B = BortThal, C = CarfilzomiLen, D = Daratumumab, E = IFN, F = Ixazomib, G = Len, H = LenPred, I = Placebo, J = Thal, K = ThalIFN. The network funnel plots shows that there exist small sample effects in the studies of ixazomib comparing placebo. CarfilzomibLen: Carfilzomib-lenalidomide; BortThal: bortezomib-thalidomide; IFN: interferon; LenPred: lenalidomide- prednisone; Thal: thalidomide; ThalIFN: thalidomide- interferon.

Figure 17. The network funnel plots of pairwise comparisons of regimens on 36 months PFS rate. Abbreviation: A = BortPred, B = BortThal, C = CarfilzomiLen, D = Daratumumab, E = IFN, F = Ixazomib, G = Len, H = LenPred, I = Placebo, J = Thal, K = ThalIFN. The network funnel plots shows that there exist small sample effects in the studies of thalidomide-interferon comparing interferon. CarfilzomibLen: Carfilzomib-lenalidomide; BortThal: bortezomib-thalidomide; IFN: interferon; LenPred: lenalidomide- prednisone; Thal: thalidomide; ThalIFN: thalidomide- interferon.

Figure 18. The network funnel plots of pairwise comparisons of regimens on 42 months PFS rate. Abbreviation: A = BortPred, B = BortThal, C = Daratumumab, D = IFN, E = Ixazomib, F = Len, G = LenPred, H = Placebo, I = Thal, J = ThalIFN. The network funnel plots shows that there exist small sample effects in the studies of thalidomide-interferon comparing interferon. BortThal: bortezomib-thalidomide; IFN: interferon; LenPred: lenalidomide- prednisone; Thal: thalidomide; ThalIFN: thalidomide- interferon.

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