Table 1.

Estimated Benefits and Risks of MM for First-line Drugs and Non-First-line Drugs

						Estimated benefit (delay in progression) [months]		Estimated risk [months]
						Drug product	Control	Drug product	Control
Experimental drug [reference]	Patient population	Date	Alias	Primary endpoint	Regulatory decision/status	Median (LCL, UCL)	Median (LCL, UCL)	Median (LCL, UCL)	Median (LCL, UCL)
First Line
Thai idomide + Dexamethasone*	1L	2006	Tha+Dex-lL-06*	ORR	Accelerated Approval	12.82 (9.56, 16.07)	7.45 (4.35, 10.56)	1.17 (0.83, 1.51)	1.36(0.91, 1.8)
Bortezomib+MP*	1L	2008	Bor+MP-lL-08*	TTP	Approved	20.9 (17.6, 24.7)	15 (14.1, 17.9)	4.09 (3.01, 5.16)	5.19 (3.82, 6.55)
Thalidomide + Dexamethasone*	1L	2008	Tha+Dex-lL-08*	TTP	Accelerated Approval	24.43 (15.47, 26.51)	7.08(6.93, 9.11)	3.04(2.16, 3.92)	2.3 (1.5, 3.11)
Lenalidomide+Dexamethasone (RD)*	1L	2014	Len+Dex-1L-14*	PFS	Approved	25.5 (20.7, 29.4)	21.2 (19.3, 23.2)	5.49 (4.45, 6.52)	4.72 (3.65, 5.8)
Non-first Line
Bortezomib*	3L	2003	Bor-3 L-03*	ORR	Accelerated Approval	6.6 (4.38, 8.82)	1.9 (1.9, 2.2)	0.18 (0.13,0.25)	0.56(0.26, 0.85)
Bortezomib*	2L	2005	Bor-2 L-05*	TTP	Approved	6.2 (4.9, 6.9)	3.5 (2.8, 4.2)	1.26(1.06, 1.45)	0.95 (0.75, 1.15)
Liposomal Doxorubicin+ Bortezomib*	2L	2007	Dox+Bor-2L-07*	TTP	Approved	9.3 (8.33, 11.27)	6.5(5.67, 7.23)	0.55 (0.24, 0.86)	0.51(0.21, 0.82)
Lenalidomide+Dexamethasone*	2L	2007	Len+Dex-2L-MM09–07*	TTP	Approved	11.1(8.68, 13.52)	4.7(2.71, 6.69)	0.81(0.65,0.99)	0.6 (0.47, 0.83)
Lenalidomide+Dexamethasone*	2L	2007	Len+Dex-2L-MM10–07*	TTP	Approved	13.1(10.23, 21.4)	5.03 (4.15, 5.18)	0.77 (0.58, 0.96)	1.08 (0.56, 1.6)
Carfilzomib*	3L	2012	Car-3 L-12*	ORR	Accelerated Approval	3.7 (2.8, 4.6)	1.9 (1.9, 2.2)	0.25 (0.18, 0.32)	0.56(0.26, 0.85)
Carfilzomib+Lenolidomide+ Low Dose Dexamethasone*	2L	2014	Car+Len+Dex-2L-14*	PFS	Approved	26.3 (23.3, 30.5)	17.6(15,20.6)	1.49 (1.12, 1.86)	1.83 (1.19, 2.47)
Panobinostat+Bortezomi b+ Dexamethasone*	2L	2014	Pan + Bor+Dex-2L-14*	PFS	Indication Refined	9.9 (8.3, 11.3)	7.7 (6.9, 8.5)	3.21(2.25,4.16)	1.48 (0.91, 2.05)
Panobinostat+Bortezomib+ Dexamethasone*	3L	2015	Pan + Bor+Dex-3L-15*	PFS	Accelerated Approval	10.6 (7.6, 13.8)	5.8 (4.4, 7.1)	2.31(1.05,3.56)	1.25 (0.41, 2.08)
Carfilzomib+Dexamethosone*	2L	2016	Car+Dex-2L-16*	PFS	Approved	18.7 (15.6, 19.96)	9.4 (8.4, 10.4)	1.24 (0.90, 1.58)	1.39 (0.90, 1.87)
Pomalidomide*	3L	2012	Pom-3 L-12*	ORR	Accelerated Approval	2.5 (1.9, 3.7)	1.9 (1.9, 2.2)	0.62 (0.36, 0.88)	0.56(0.26, 0.85)
Pomalidomide + dexamethasone*	3L	2012	Pom+ Dex-3 L-12*	ORR	Not Used	3.8 (3.2, 4.9)	1.9 (1.9, 2.2)	0.62 (0.36, 0.89)	0.56(0.26, 0.85)
Pomalidomide + Dexamethasone (Low Dose)*	3L	2014	Pom + Dex-3L-14*	PFS	Approved	4(3.6, 4.7)	1.9 (1.9, 2.2)	0.38 (0.26, 0.5)	0.56(0.26, 0.85)
Daratumab 16 mg*	4L	2015	Dar-4L-MMY-15*	ORR	Accelerated Approval	5.29 (2.37, 8.21)	1.9 (1.9, 2.2)	0.23 (0.12, 0.34)	0.56(0.26, 0.85)
Daratumumab 16 mg*	4L	2015	Dar-4L-GEN-15*	ORR	Accelerated Approval	7.49 (2.6, 12.37)	1.9 (1.9, 2.2)	0.23 (0.12, 0.34)	0.56 (0.26, 0.85)
Daratumumab+Bortezomib+Dexamethasone*	2L	2016	Dar+Bor+Dex-2L-16*	PFS	Approved	23.41(21.84, 24.98)	7.2 (6.2, 7.9)	2.21 (1.26, 3.16)	2.41 (1.24, 3.58)
Daratumumab+Lenalidomide+Dexamethasone*	2L	2016	Dar+Len + Dex-2L-16*	PFS	Approved	26.78(25.78, 27.79)	18.4(13.9, 20.07)	3.39 (2.11, 4.68)	3.23 (1.9, 4.56)
Elotuzumab+LD*	2L	2015	Elo+Len + Dex-2L-15*	PFS, ORR	Approved	19.4(16.6, 22.2)	14.9 (12.1, 17.2)	2.6(1.95,3.25)	3.31 (2.31, 4.32)
Ixazomib + LD*	2L	2015	lxa + Len + Dex-2L-15*	PFS	Approved	20.6 (17, 22.04)	14.7 (12.9, 17.6)	1.53 (0.94, 2.13)	2.2 (1.4, 2.99)

^*indicates a pivotal trial.

Confidence intervals are 95% confidence intervals. Date field shows year of publication of the reference. In the “Design” field in the table above “H-H” means Head-to-Head trial; “A-O” means Add-on trial; “SA” means Single Arm trial. Panobinostat plus Bortezomib plus Dexamethasone analyses of 2014 and 2015 are both based on the same trial 2308 (as mentioned in the Study column in the table above). However, the 2015 analysis is for a subpopulation.