Table 7.

Feasibility testing of the ESMO-MCBS v1.1 for first-line multiple myeloma (n=8)

Medication	Trial name	Setting	Primary outcome	PFS/DFS control	PFS/DFS gain	PFS/DFS HR	OS control	OS gain	OS HR	RR	QOL	Toxicity	ESMO-MCBS score	ESMO-MCBS form	Reference(s)
VTD versus TD or VBMCP/VBAD/B	GEM2005-less65 PETHEMA/GEM	ASCT eligible	CR post ASCT (PFS)									More neuropathy but not meeting criteria for downgrading		1/2b	76
			TD	28.2 months	28.0 months	p=0.01	65% at 4 years	9%	NS	CRR 46% vs 24%, gain 22%			C/not scoreable
			VBMCP/VBAD/B	35.3 months	20.9 months	p=0.01	70% at 4 years	4%	NS	CRR 46% vs 38%, gain 8%			NEB/not scoreable
VTD versus TD	GIMEMA 2005	ASCT eligible	CR post induction (PFS)	56% at 3 years	12%	0.63 (0.45– 0.88)	84% at 3 years	2%	NS	(near) CRR 31% vs 11%, gain 20%		More neuropathy but not meeting criteria for downgrading	C/not scoreable	1/2b	77
																VCD versus PAD	MM5	ASCT eligible	Non-inferiority of ≥VGPR rates (margin: −10%)							VGPR difference: 2.8% (−6.8% to 12.3%) non-inferiority met		SAEs higher in the control arm	Not scoreable	1/2 c	78
VMP versus MP	VISTA	ASCT ineligible	TTP	16.6 months	7.4 months	0.48 (p<0.001)	43.1 months	13 months	0.70 (0.57– 0.85)				4	2a	79 80
VMPT versus VMP	GIMEMA VMPT	ASCT ineligible	PFS	27 months 41% at 3 years	>13 months 15%	0.67 (0.50– 0.90)	87% at 3 years	2%	NS		–	Vascular and cardiac events increased in experimental arm (−1 point)	2	2b	81
Lenalidomide-d continuous versus x18 or MPT x12	FIRST	ASCT ineligible	PFS												82
			Len-d x18	20.7 months	4.8 months	0.70 (0.60–0.82)	56% at 4 years	3% gain at 4 years	NS				3	2b
			MPT	21.2 months	4.3 months	0.72 (0.61–0.85)	47 months 51% at 4 years	7 months 8% gain at 4 years	0.78 (0.64– 0.96)				4	2a
VMP ± daratumumab	ALCYONE	ASCT ineligible	PFS	18 months 50% at 18 months	9+ months 21% at 18 months	0.50 (0.38–0.65)						More infections but not meeting criteria for penalty	3	2b	83
Lenalidomide-d ± bortezomib	SWOG S07777	ASCT ineligible	PFS	30 months	13 months	0.71 (0.56–0.91)	64 months	11 months	0.71 (0.52– 0.96)			Slightly increased	4	2a	84

ASCT, autologous stem cell transplantation; CR, complete remission; CRR, complete remission rate; d, dexamethasone; DFS, disease-free survival;ESMO-MCBS v1.1, European Society for Medical Oncology—Magnitude of Clinical Benefit Scale, version 1.1; Len-d, lenalidomide-d; MP, melphalan and prednisone; MPT, melphalan, prednisone and thalidomide; NEB, no evaluable benefit; NS, not significant; OS, overall survival; PAD, bortezomib, doxorubicin, dexamethasone;PFS, progression-free survival; QOL, quality of life; RR, response rate; SAE, serious adverse event; TD, thalidomide and dexamethasone; TTP, time to progression; VBMCP/VBAD/B, vincristine, BCNU, melphalan, cyclophosphamide, prednisone/vincristine, BCNU, doxorubicin, dexamethasone/bortezomib; VCD, bortezomib, cyclophosphamide, dexamethasone; VGPR, very good partial response rate; VMP, bortezomib, melphalan and prednisone; VMPT, bortezomib, melphalan, prednisone and thalidomide; VTD, bortezomib, thalidomide and dexamethasone.