Managing multiple myeloma in the elderly: are we making progress?

Figures & data

Table 1. Examples of induction regimens for elderly patients not eligible for high-dose therapy and autologous stem-cell transplantation.

Regimen	Study	Regimen details	Result	Ref.
MPT	GIMEMA	Melphalan 4 mg/m^2 p.o. daily, days 1–7 Prednisone 40 mg/m^2 daily, days 1–7 Thalidomide 100 mg p.o. daily Cycles repeated every 4 weeks × 6, thalidomide continued until relapse	ORR ∼85%, CR 15.6% Median TTP 24.7 months	[38]
	IFM 99-06	Melphalan 0.25 mg/kg p.o. daily, days 1–4^† Prednisone 2 mg/kg p.o. daily, days 1–4 Thalidomide 200 mg p.o. daily (dose increased as tolerated to maximum 400 mg) Cycles repeated every 6 weeks × 12, then stopped	ORR 76%, CR 13% Median OS 51 months	[39]
MPV	VISTA	Melphalan 9 mg/m^2 p.o. daily, days 1–4 Prednisone 60 mg/m^2 p.o. daily, days 1–4 Bortezomib 1.3 mg iv. days 1, 4, 8, 11, 22, 25, 29 and 32 during cycles 1–4, and on days 1, 8, 22 and 29 during cycles 5–9 Cycles repeated every 6 weeks × 9, then stopped	ORR 76%, CR 30% Median duration of response 19.9 months Median OS not reached at median follow-up of 16 months	[6,18]
VMP versus VTP		Melphalan 9 mg/m^2 p.o. daily, days 1–4 Prednisone 60 mg/m^2 p.o. daily, days 1–4 Bortezomib 1.3 mg/m^2 iv. days 1, 4, 8, 11, 22, 25, 29 and 32 during cycle 1, and on days 1, 8, 22 and 29 during cycles 2–6 versus Thalidomide 100 mg p.o. daily (50 mg days 1–15) Prednisone 60 mg/m^2 p.o. daily, days 1–4 Bortezomib 1.3 mg/m^2 iv. on days 1, 4, 8, 11, 22, 25, 29 and 32 during cycle 1, and on days 1, 8, 22 and 29 during cycles 2–6 After four cycles of induction, patients were randomized to receive VT or VP as maintenance until disease progression	Postinduction (VMP): ORR 80%, CR 20% Postinduction (VTP): ORR 81%, CR 28% No difference in efficacy between VMP and VTP; VMP better tolerated CR rates further improved with maintenance VT (CR 44%) or VP (CR 39%)	[32]
MPR-R	MM-015	Melphalan 0.18 mg/kg p.o. daily, days 1–4 Prednisone 2 mg/kg p.o. daily, days 1–4 Lenalidomide 10 mg p.o. daily Cycles repeated every 4 weeks × 9 ± lenalidomide continued until relapse	MPR-R: ORR 77%, CR 16% Median TTP 24.7 months 2-year OS 86.2%	[65]
VMPT-VT		Thalidomide 50 mg p.o. daily Melphalan 9 mg/m^2 p.o. daily, days 1–4 Prednisone 60 mg/m^2 p.o. daily, days 1–4 Bortezomib 1.3 mg/m^2 iv. daily, days 1, 4, 8, 11, 22, 25, 29 and 32 during cycles 1–4, and on days 1, 8, 22 and 29 during cycles 5–9 Cycles repeated every 6 weeks × 9, followed by maintenance with: Bortezomib 1.3 mg/m^2 iv. every 14 days Thalidomide 50 mg p.o. daily Continued for 2 years or until progression/relapse, whichever is earlier	ORR 89%, CR 38% Responses were superior compared with VMP at the cost of greater toxicity Grade 3 or 4 neutropenia 38% and cardiologic events 10%	[33]
Lenalidomide–bortezomib–dexamethasone		Lenalidomide 25 mg p.o. daily, days 1–14 Bortezomib 1.3 mg/m^2 iv. days 1, 4, 8 and 11 Dexamethasone 20 mg (10 mg for cycles 5–8) p.o. on days 1, 2, 4, 5, 8, 9, 11 and 12 Cycles repeated every 3 weeks × 8 followed by ASCT (after a minimum of four cycles) or further maintenance with: Lenalidomide 25 mg p.o. daily, days 1–4 Bortezomib 1.3 mg/m^2 iv. on days 1 and 8 Dexamethasone 10 mg p.o. on days 1, 2, 8 and 9	Phase II cohort (n = 35): ORR 100%, CR 37%	[57]

Nonmelphalan-containing induction regimens used in patients proceeding to ASCT can also be used in patients not proceeding to ASCT.

^†Consider using a lower dose of melphalan (0.18–2.0 mg/kg) and thalidomide (50–100 mg) for patients aged ≥75 years [63].

ASCT: Autologous stem-cell transplantation; CR: Complete response; GIMEMA: Gruppo Italiano Malattie Ematologiche dell’Adulto; IFM 99-06: Francophone Myeloma Intergroup 99-06; iv.: Intravenous; MPR: Melphalan, prednisone and lenalidomide; MPR-R: Melphalan, prednisone and lenalidomide followed by lenalidomide maintenance; MPT: Melphalan, prednisone and thalidomide; MPV: Melphalan, prednisone and bortezomib; ORR: Overall response rate; OS: Overall survival; p.o.: Per oral; TTP: Time to progression; VISTA: Velcade as Initial Standard Therapy in Multiple Myeloma: Assessment with Melphalan and Prednisone; VMP: Bortezomib, melphalan and prednisone; VMPT-VT: Bortezomib, melphalan, prednisone and thalidomide followed by bortezomib and thalidomide maintenance therapy; VP: Bortezomib and prednisone; VT: Bortezomib and thalidomide; VTP: Bortezomib, thalidomide and prednisone.

Table 2. Phase III studies comparing melphalan and prednisone with melphalan, prednisone and thalidomide for the upfront treatment of multiple myeloma.

Study	Regimen	Participants (n)	CR and PR (%)	TTP	OS	Statistical significance for OS	Ref.
GIMEMA	MPT (T maintenance to PD)	129	76	21.8	45		[19]
	MP (no maintenance)	126	48	15.5	47.6	NS
IFM 99	MPT (72 weeks treatment)	191	76	27.5	51.6		[39]
	MP (72 weeks treatment)	124	35	17.8	33.2
	MEL 100	121	65	19.4	38.3
IFM 01	MPT (72 weeks treatment)	113	62	24.1	45.3	p = 0.03	[61]
	MP (72 weeks treatment)	116	31	9	27.7
NMSG	MPT (T maintenance)	148	47 (23% ≥VGPR)	20	29	NS	[60]
NMSG	MP	179	40 (7% ≥VGPR)	18	33
HOVON	MPT (T maintenance)	165	66	PFS: 15	40	p = 0.05	[104]
HOVON	MP	168	45	PFS: 11	31
Beksac et al. (2011)	MPT (eight cycles)	62	58	DFS: 21	26	NS	[62]
	MP (eight cycles)	60	38	DFS: 14	28

CR: Complete response; DFS: Disease-free survival; GIMEMA: Gruppo Italiano Malattie Ematologiche dell’Adulto; HOVON: Dutch–Belgian Hemato-Oncology Cooperative Group; IFM: Francophone Myeloma Intergroup; MEL 100: Melphalan 100 mg/m²; MP: Melphalan and prednisone; MPT: Melphalan, prednisone and thalidomide; NMSG: Nordic Myeloma Study Group; NS: Not significant; OS: Overall survival; PD: Progressive disease; PFS: Progression-free survival; PR: Partial response; T: Thalidomide; TTP: Time to progression; VGPR: Very good partial response.

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