First line vs delayed transplantation in myeloma: Certainties and controversies

Table 2 Improved outcomes with the introduction of novel agents in the upfront treatment of multiple myeloma

Ref.	Publication’s year	Therapy	Patients n	≥VGPR (%) preASCT	≥VGPR (%) postASCT	≥PR %	CR/nCR %	PFS/EFS OS
Thalidomide
Rajkumar et al[32]	2006	TD vs D	200	63 vs 41 (≥ PR)	NR			NR
Cavo et al[10]	2009	TD vs VAD	270	30 vs 15	68 vs 49			PFS 51% vs 31% at 4 yr
								OS 69% vs 53% at 5 yr
Barlogie et al[17]	2006	TT2 + Thal vs TT2	668	NR	62 vs 43			EFS 56% vs 44% at 3 yr
								OS 65% vs 65% at 5 yr
Lokhorst et al[33]	2010	TAD vs VAD	402	32 vs 15	49 vs 32			EFS 34 mo vs 22 mo
								OS 73 mo vs 60 mo
Lenalidomide
Richardson et al[38]	2010	VRD	35			100	57	NR
Palumbo et al[56]	2014		402
		MPR	202			NR	NR	PFS 22.4 mo vs 43 mo
		vs
		HDM	200			NR	NR	OS 65.3% vs 81.6%
		Maintenance R	198			78	23	PFS 41.9 mo vs 21.6 mo
		vs
		No maintenance	204			77	19	OS 79% vs 88%
McCarthy et al[66]	2012	Lenalidomide vs placebo	460					PFS at 3 yr
								66% vs 39%
								OS at 3 yr
								88% vs 80%
Attal et al[67]	2012	Lenalidomide vs placebo	614					PFS at 4 yr
								43% vs 22%
								OS at 4 y
								73% vs 75%
Bortezomib
Harousseau et al[16]	2010	®VD vs VAD	482	38 vs 15	54 vs 37			36 m vs 27 m
Sonneveld et al[34]	2012	®Induction PAD + maint VEL vs induction VAD + maint Thal	626	NR	75 vs 61			46% vs 42% at 3 yr
Cavo et al[13]	2010	®VTD vs TD induction and consolid	480	62 vs 28	82 vs 64			68% vs 56% at 3 yr
Rosiñol et al[37]	2012	®VTD vs TD	202	29 vs 14 (CR)	59 vs 40 (CR)			82% at 2 yr (OS)
Moreau et al[35]	2011	®VD vs vtD	199	49 vs 39	74 vs 58			30 mo vs 26 mo
Leleu et al[36]	2013	VTd-ASCT + consolid VTd vs VTd-ASCT	217	After treatment: 83 vs 64				TTP: 62% vs 29% at 4 yr

VGPR: Very good partial response; TTP: Time to progression; PFS: Progression free survival; NR: Not reported; Thal: Thalidomide; TD: Thalidomide dexamethasone; VAD: Vincristine adriamycin dexamethasone; TAD: Thalidomide adriamycin dexamethasone; MPR: Melphalan prednisone lenalidomide; VTD: Bortezomib thalidomide dexamethasone; VD: Bortezominb dexamethasone; PAD: Adriamycin bortezomib dexamethasone; vtD: Reduced doses bortezomib thalidomide dexamethasone; R: Lenalidomide; VRD: Bortezomib lenalidomide dexamethasone; OS: Overall survival; ASCT: Autologous transplantation; nCR: Near CR; HDM: High dose melphalan; Consolid: Consolidation; Maint: Maintenance.