Multiple myeloma: optimal management and long-term disease control

Figures & data

Table 1 Survival times associated with cytogenetic groups defined by FISH in the Medical Research Council Myeloma IX study

FISH lesion	PFS with lesion (months)	PFS without lesion (months)	OS with lesion (months)	OS without lesion (months)
Hyperdiploidy	18.9	17.8	49.7	43.7
t(4;14)*	13.1	19.3	27.7	50.9
t(11;14)*	21.3	17.5	51.6	46.9
t(14;16)*	13.6	18.6	32.9	48.3
+ 1q**	13.8	22.1	31.0	54.8
17p deletion***	14.7	18.3	26.7	48.5

Notes: Data from Boyd et al.⁶

* Represents translocation between the two chromosomes.

** Represents gain of function mutation involving the q arm in chromosome 1.

*** Represents deletion of a gene affecting p53 function on the p arm in chromosome 17.

Abbreviations: Iq, chromosome I chain; FISH, fluorescence in situ hybridization; PFS, progression-free survival; OS, overall survival; t, translocation.

Figure 1 Overall survival graded by number of adverse lesions. Those with adverse IgH translocation, +1q, and 17p deleletion had the worst overall survival.⁶

Table 2 Definition and survival of combined FISH and ISS risk groups

Group	Combined FISH and ISS risk group	Median OS (months)
ISS I and no lesions	Favorable risk	67.8
ISS I and I lesion
ISS II and no lesion
ISS I and > I lesion	intermediate risk	41.3
ISS II and I lesion
ISS III and no lesion
ISS III and I lesion
ISS II and > I lesion	Ultra-high risk	19.4
ISS III and > I lesion

Note: Data from Boyd et al.⁶

Abbreviations: FISH, fluorescence in situ hybridization; ISS, International Staging System; OS, overall survival.

Table 3 Summary of Phase II/III trials in transplant-eligible patients

Author, year	Drug combinations	ORR (>PR) after induction (%)	Median PFS months	Median OS months
Cavo et al, 2005^Citation19	TD vs	76	NA	NA
	vad	52	NA	NA
Rajkumar et al, 2006^Citation20	TD vs	61	6.5	NA
	dexamethasone	41	14.9	NA
Lokhorst et al, 2010^Citation21	TAD vs	71	34	73
	vad	57	22	60
Morgan et al, 2012^Citation15	CTD vs	82.5	27	NR (range 0–74)
	cvad	71.2	25	63 (range 1–73)
Jagannath et al, 2005^Citation26	vd	88	NA	Est 12, (87%)*
	(patients received bortezomib alone for the first two cycles then VD for cycles 3–6)	NA	NA	NA
Harousseau et al, 2010^Citation27	Bortezomib-dexamethasone vs	78.5	36	NR
	VAD	62.8	29.7	NR
Reeder et al, 2009^Citation28	CVD	88	NA	NA
Sonneveld et al, 2012^Citation29	PAD vs	78	35	60, (61%)*
	VAD	54	28	60, (55%)*
Cavo et al, 2010^Citation30	VTD vs	93	36, (68%)*	36, (86%)*
	TD	79	36, (56%)*	36, (84%)*
Sonneveld et al, 2013^Citation34	Carfilzomib + Td	96	(74% of 70 patients)*	(7% of 70 patients)*
Rajkumar et al, 2010^Citation35	Rd vs	70	25.3	(96%)*
	RD	81	19.1	(87%)*
Pawlyn et al, 2013^Citation36	CRD vs	83	NA	NA
	CRDa	73	NA	NA
Richardson et al, 2010^Citation37	VRD	100	Est 18, (75%)*	Est 18, (97%)*
Roussel et al, 2010^Citation38	VRD	97	NA	NA
Kumar et al, 2012^Citation39	CVD vs	75	12, (93%)*	12, (100%)*
	CVRD vs	88	(86%)*	(92%)*
	VRD	85	(83%)*	(100%)*
Jakubowiak et al, 2012^Citation40	Carfilzomib + Rd	97	Est 24, (92%)*	NA
Korde et al, 2013^Citation41	Carfilzomib + RD-R	96	10, (follow-up 83.3%)*	NA
Moreau et al, 2011^Citation31	VTD vs	88	26**	NA
	VD	81	30**	NA

Notes:

* Some of the trials had fixed follow-up at 36 months, hence why some of the data is shown as percentage.

** High variability in treatment administered post ASCT in both groups.

Abbreviations: CRD,cyclophosphamide–lenalidomide–dexamethasone; CRDa, attenuated dose of cyclophosphamide–lenalidomide–dexamethasone; CTD, cyclophosphamide–thalidomide–dexamethasone; CVAD, cyclophosphamide–bortezomib–doxorubicin–dexamethasone; CVD, cyclophosphamide–bortezomib–dexamethasone; CVRD, cyclophosphamide–bortezomib–lenalidomide–dexamethasone; Est, estimated; NA, not assessed; NR, not reached; ORR, overall response rate; OS, overall survival; PAD, bortezomib–doxorubicin–dexamethasone; PFS, progression-free survival; PR, partial response; Rd, lenalidomide–low-dose dexamethasone; RD, lenalidomide–dexamethasone; RD-R, lenalidomide–dexamethasone followed by lenalidomide maintenance; TAD, thalidomide–doxorubicin–dexamethasone; Td, thalidomide–low-dose dexamethasone; TD, thalidomide–dexamethasone; VAD, vincristine–doxorubicin–dexamethasone; VD, bortezomib–dexamethasone; vs, versus; VRD, bortezomib–lenalidomide–dexamethasone; VTD, bortezomib–thalidomide–dexamethasone.

Table 4 Phase III trials in non-transplant-eligible patients

Author, year	Regimen (number of patients)	CR (%)	>VGPR (%)	ORR (%)	Median PFS (months)	Median OS (months)
Palumbo et al, 2008^Citation52	MPT (167)	15.6	29.3	68.9	21.8	45
	MP (164)	3.7	11	47.6	14.5	47.6
Facon et al, 2007^Citation53	MPT (125)	13	47	76	27.5	51.6
	MP (196)	2	7	35	17.8	33.2
	Reduced-intensity ASCT (126)	18	43	65	19.4	38.3
Waage et al, 2010^Citation54	MPT (182)	13	23	57	15	29
	MP (175)	4	7	40	14	32
Wijermans et al, 2010^Citation55	MPT (165)	Unava1lable as immunofixation not performed on all patients	27	66	13	40
	MP (168)		10	45	9	31
Hulin et al, 2009^Citation56	MPT (117)	7	21	62	24.1	44
	MP (115)	1	7	31	18.5	29.1
Morgan et al, 2011^Citation58	CTDa (426)	13.1	16.9	63.8	13	33.2
	MP (423)	2.4	1.7	32.6	12.4	30.6
San Miguel et al,	VMP (344)	33	71	NA	21.7	NR
2008/2013^Citation59,Citation60	MP (338)	4	35	NA	15.2	NR
Palumbo et al, 2008^Citation62	VMPT (193)	31	55	NA	24, 86.8%*	36, 89.5%*
	VMP (200)	16	42	NA	24, 78.1%*	36, 88.7%*
Mateos et al, 2012^Citation63	VMP (80)	18	NA	78	NA	NA
	VTP (87)	23	NA	78	NA	NA
Larocca et al, 2013^Citation64	VP (51)	NA	NA	67	14	12, 80%*
	VCP (51)	NA	NA	63	16	12, 82%*
	VMP (50)	NA	NA	80	16	12, 80%*
Rajkumar et al, 2010^Citation35	Rd (222)	4	26	70	25.3	12, 96%*
	RD (223)	5	33	81	19.1	12, 87%*
Palumbo et al, 2007^Citation65	MPR (54)	47.6	NA	81	12, 92.3%*	12, 100%*
Palumbo et al, 2012^Citation66	MP (154)	3.2	9.1	50	13	NR
	MPR (153)	3.3	29.4	68	14	NR
	MPR-R (152)	9.9	23.0	77	31	45.2

Note:

* The percentage values represent the proportion of patients who were alive within each treatment group after a fixed follow-up period.

Abbreviations: ASCT, autologous stem cell transplantation; CR, complete remission; CTDa, attenuated dose of cyclophosphamide–thalidomide–dexamethasone; MP, melphalan–prednisone; MPR, melphalan–prednisone–lenalidomide; MPR-R, melphalan–prednisone–lenalidomide followed by lenalidomide maintenance; MPT, melphalan–prednisone–thalidomide; NA, not assessed; NR, not reached; ORR, overall response rate; OS, overall survival; PFS, progression-free survival; Rd, lenalidomide–low-dose dexamethasone; RD, lenalidomide–dexamethasone; VCP, bortezomib–cyclophosphamide–prednisone; VGPR, very good partial response; VMP, bortezomib–melphalan–prednisone; VMPT, bortezomib–melphalan–prednisone–thalidomide; VP, bortezomib–prednisone; VTP, bortezomib–thalidomide–prednisone.

Table 5 Dose adjustment levels

Agent	Dose level 0	Dose level 1	Dose level 2
Dexamethasone	40 mg/day on days 1, 8, 15, and 22 every 4 weeks	20 mg/day on days 1, 8, 15, and 22 every 4 weeks	10 mg/day on days 1, 8, 15, and 22 every 4 weeks
Melphalan	0.25 mg/kg on days 1–4 every	0.18 mg/kg on days 1–4 every	0.13 mg/kg on days 1–4 every
	4–6 weeks	4–6 weeks	4–6 weeks
Thalidomide	100 mg/day	50 mg/day	50 mg every other day
Lenalidomide	25 mg/day on days 1–21 every	15 mg/day on days 1–21	10 mg/day on days 1–21 every
	4 weeks	every 4 weeks	4 weeks
Bortezomib	1.3 mg/m^2 twice weekly on days	1.3 mg/m^2 once weekly on days	1.0 mg/m^2 once weekly on days
	1, 4, 8, and 11 every 3 weeks	1, 8, 15, and 22 every 5 weeks	1, 8, 15, and 22 every 5 weeks

Note: Data from Palumbo et al.⁶⁸

Figure 2 Risk factors and adapted treatment approaches for elderly patients.

Adapted from International Myeloma Working Group Guidelines.⁴⁷

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