Table 1.

Selected bortezomib regimens in treatment of MM

Reference	FDA/NCCN	Patient population	Patients	Regimen	Best response	Survival data
Jagannath et al²⁶	N/Y – (Cat 1)	Previously untreated	32	Bor 1.3 mg/m² on D1, 4, 8, & 11 for 6–3 wk cycles	88% ORR	OS 1 yr—87%
				Dex (40 mg/d of/after) for ≤PR after 2 cycles; ≤CR after 4 cycles	25% CR/nCR
Harousseau et al²⁷	N/Y – (Cat 1)	Previously untreated	48	Bor 1.3 mg/m² on D1, 4, 8, & 11 for 4–3 wk cycles	66% ORR	NR
				Dex 40 mg on D1–4, 9–12 on C1 & 2; D1–4 on C3 & 4	21% CR
				Consolidation to auto-SCT	10% VGPR
Rosinõl et al²⁸	N/Y – (Cat 1)	Previously untreated	40	Bor 1.3 mg/m² on D1, 4, 8, & 11 for 6–3 wk cycles	77.5% ORR	NR
				Dex 40 mg on D1–4, 9–12, 17–20 on C2, 4, & 6	12.5% CR
				Consolidation to auto-SCT	7.5% VGPR
Richardson et al²⁹	N/N	Previously untreated	64	Bor 1.3 mg/m² on D1, 4, 8, & 11	63% ORR	Med PFS—17 mos
				Max 8–3 wk cycles or 2 cycles past CR	9% CR/nCR	OS 2.5 yrs—79%
					8% VGPR
Dispenzieri et al²²	N/N	Previously untreated	39	Bor 1.3 mg/m² on D1, 4, 8, & 11 for 8–3 wk cycles	51% ORR	PFS 2 yrs—16%
		High risk per protocol		Maintenance D1, 15 of 28 d cycle	0% CR	OS 2 yrs—76%
				Reinduction at PD	10% VGPR
Popat et al³⁰	Y/Y – (Cat 1)	Previously untreated	41	PAD1 (phase I)	62% ≥VGPR	PFS—29 v 24 mos
		–Induction regimen		Bor 1.3 mg/m² on D1, 4, 8, & 11 for 4–3 wk cycles	42% ≥VGPR	OS 1 yr−100% v 95%
		–Phase I/II		Doxo 0, 4.5, 9 mg/m² on D1–4 to max admin dose	(PAD1 v 2 – induction)
				Dex 40 mg on D1–4, 8–11, 15–18—C1, D1–4—C2–4 PAD2 (phase II)
				Bor 1 mg/m² on D1, 4, 8, & 11 for 4–3 wk cycles	81% ≥VGPR	OS 2 yrs
				Doxo 9 mg/m² on D1–4	53% ≥VGPR	−95% v 73%
				Dex 40 mg D1–4, 8–11, 15–18—C1, D1–4—C2–4	(PAD1 v 2 – posttransplant)
				Consolidation w/auto-SCT
Cavo et al³¹	N/Y – (Cat 1)	Previously untreated	474	Bor 1.3 mg/m² on D1, 4, 8, & 11 for 3–3 wk cycles	19% CR^*	PFS 2 yrs—85%^*
		Induction regimen		Thal 200 mg/d on D1–63	62% ≥ VGPR^*	OS 20 mos—93%
		Phase III trial		Dex 40 mg D1, 2, 4, 5, 8, 9, 11, 12	Postinduction
				Consolidation w/auto-SCT × 2→ VTD × 2- 35 d cycle	44% CR^*
				Compared to TD→ auto-SCT × 2→ TD × 2- 35 d cycle	80% ≥ VGPR^*
					Full treatment
Palumbo et al³²	N/N	Previously untreated	102	Bor 1.3 mg/m² on D1, 4, 8, & 11 for 4– 3 wk cycles	13% CR	PFS 2 yrs—69%
		Induction regimen		PLD 30 mg/m² on D4	58% ≥VGPR	OS 2 yrs—86%
		Phase II		Dex 40 mg D1–4, 8–11, 15–18—C1, D1–4—C2–4	Postinduction
				Consolidation w/tandem auto-SCT w/MEL100	38% CR
				Followed by Len/Pred→ maintenance Len	82% ≥VGPR
					Posttransplant
Moreau et al³³	N/N	Previously untreated	205	Bor 1 mg/m² on D1, 4, 8, & 11 for 4–3 wk cycles	31% CR/nCR	NR
		Induction regimen		Thal 100 mg/d on D1–21	50% ≥ VGPR^*
		Phase III trial		Dex 40 mg D1–4, 8–11	Postinduction
				Consolidation w/auto-SCT	60% CR/nCR
				Compared to standard VTD regimen above	66% ≥ VGPR^*
					Post 1st ASCT
Roussel et al³⁴	N/N	Nonprogressive MM after induction	53	Bor 1 mg/m² on D-6, −3, +1, +4	32% CR	Median PFS-NR
		Conditioning reg.		MEL200 on D-2	70% ≥VGPR	PFS 2 yrs—76%
		Phase II trial		Auto-SCT reinfusion on D0	Posttransplant
Harousseau et al³⁵	N/Y – (Cat 1)	Previously untreated	482	Bor 1.3 mg/m² on D1, 4, 8, & 11 for 4–3 wk cycles	15% CR/nCR^*	PFS—36 mos
		Induction regimen		Dex 40 mg D1–4, 9–12 on C1 & 2; D1–4 on C3 & 4	38% ≥ VGPR^*	OS 3 yrs—81%
		Phase III trial		Consolidation w/auto-SCT ± DCEP	79% ORR^*
				Compared to VAD induction	Postinduction
					35% CR/nCR^*
					54% ≥ VGPR^*
					Post 1st ASCT
Bruno et al³⁶	N/N	Relapse s/p AlloSCT	23	Bor 1–1.3 mg/m² on D1, 4, 8, & 11 4-wk cycles	61% ORR	PFS—6 mos
		Retrospective		±Dex 20–40 mg on D1, 4, 15, and 18	22% CR	OS 6 mos—91%
Kröger et al³⁷	N/N	Post-allo-SCT	18	Bor 1.3 mg/m² on D1, 4, 8, & 11 for 2–3 wk cycles	30% CR	NR
		Enhance/maintain remission			50% PR
					20% Min Res (10 patients w/residual dz)
Kröger et al³⁸	N/N	Post-allo-SCT	8	Bor 1.3 mg/m² on D1, 4, 8, & 11 for 4–3 wk cycles	59% CR	PFS 5 yrs—53%
		DLI + Bor/Thal/Len		Patients received median of 2 cycles (1–5)		OS 5 yrs—90%
						(no specific Bor data mentioned)
Sonneveld et al³⁹	N/N	Maintenance	833	Bor 1.3 mg/m² every 2 wks for 2 yrs	CR 15→ 27%	NR
		Phase III trial		VAD v. PAD induction→ auto-SCT × 1–2→ Thal 50 mg/d (VAD arm) vs. Bor (PAD arm)
Rosinõl et al⁴⁰	N/N	Maintenance	390	Bor/Thal Maintenance for planned 3 yrs	NR	NR
				No doses noted in literature/clinical trials.gov
				Compared to Thal alone and IFN
Palumbo et al⁴¹	N/N	Maintenance	511	Bor/Mel/Pred/Thal induction	Maintenance did not improve RR	NR
				Bor 1.3 mg/m² every 2 wks
				Thal 50 mg/d
Ladetto et al⁴²	N/N	Consolidation/maintenance	40	Bor 1.6 mg/m² on D1, 8, 15, 22 for 4–5 wk cycles	CR 15→ 49%	PFS—60 mos
				Thal 50 mg/d→ 200 mg/d; increase weekly as tolerated	MR 3→ 18%	OS 3 yrs—89%
				Dex 20 mg D1–4, 8–11, 15–18
Nair et al²⁵	N/N	Maintenance	177	Bor 1 mg/m² on D1, 4, 8, & 11 monthly for 1 yr	NR	NR
				Bor 1 mg/m² weekly for 2 yrs
				Combined with Len/Dex for planned all 3 yrs
Kumar et al⁴³	N/N	Maintenance	117	Bor 1.3 mg/m² on D1, 8, 15, & 22 for 4–42 d cycles	NR	NR
Richardson et al⁴⁴	N/N	Maintenance	68	Bor on D1 & 8 every 3 wks	NR	NR
				Combined with Len/Dex
				No duration noted in article
Mateos et al⁴⁵	N/N	Maintenance	260	Bor/Thal/Pred v Bor/Mel/Pred Induction	CR	NR
				Bor 1.3 mg/m² on D1, 4, 8, & 11—3-wk cycle	VP: 39%
				Given every 3 mos for 3 yrs	VT: 44%
				Plus either Pred/Thal

Statistically significant difference between control and treatment groups

DLI, donor lymphocyte infusion.