Role of combination bortezomib and pegylated liposomal doxorubicin in the management of relapsed and/or refractory multiple myeloma

Figures & data

Table 1 Subgroup analyses from phase III trial of bortezomib vs pegylated liposomal doxorubicin + bortezomib (PLD+B)

Subgroup	ORR (%)		TTP (days)		p value
	B	PLD+B	B	PLD+B
Age ≥ 65 yrs	39	49	205	276	0.0056
β2-microglobulin ≥5.5mg/L	33	49	178	276	0.0007
Primary refractory disease	48	43	189	MNR	0.0322
No prior ASCT	39	45	197	331	0.0009
Prior ASCT	46	50	197	276	0.0011
≥2 prior lines of therapy		N/A	186	276	<0.0001
1 prior line of therapy		N/A	199	330	0.036
Anthracycline naïve		N/A	197	282	0.015
Anthracycline exposed		N/A	197	295	0.0001
ISS stage 3		N/A	177	276	<0.0007
ISS stage 2		N/A	186	250	<0.004
ISS stage 1		N/A	223	331	0.067
TSD >2 years		N/A	197	295	<0.0001
TSD ≤2 years		N/A	197	243	0.0033
Relapse <12 months post	74	93	205	276	0.13
ASCT		(p = 0.01)

Abbreviations: ASCT, autologous stem cell transplant; ISS, International Staging System; MNR, median not reached; N/A, not available; TSD, time since diagnosis; TPP, time to disease progression; ORR, overall response rate.

Table 2 Grade 3–4 adverse events in phase III trial of bortezomib vs pegylated liposomal doxorubicin + bortezomib (PLD+B)

Adverse event	Bortezomib (%) N = 318	PLD+B (%) N = 318	p value
All drug-related adverse events	165 (52)	217 (68)	<0.001
Thrombocytopenia	49 (16)	71 (23)	0.249
Neutropenia	46 (15)	94 (29)	<0.001
Febrile neutropenia	2 (2)	3 (3)	n/a
Peripheral neuropathy	39 (9)	35 (4)	n/a
Cardiotoxicity	7 (3)	10 (2)	n/a
Thromboembolic events	1 (1)	1 (1)	n/a
Diarrhea	14 (4)	22 (7)	0.034
Palmar plantar erythrodysesthesia	0 (0)	15 (5)	<0.001

Table 3 Pegylated liposomal doxorubicin + bortezomib combinations in relapsed/refractory setting

Author	Phase of study	Regimen	Dose	Evaluable pts (#)	PR (%)	CR/nCR (%)	PFS/TTP (med. months)
Orlowski^Citation22	I	B-PLD	B 0.9–1.5 mg/m^2 d 1, 4, 8, 11 PLD 30 mg/m^2 d 4	22	36	36	9.3 (TTP)
Orlowski^Citation22	III	B vs B-PLD	B 1.3 mg/m^2 d 1, 4, 8, 11 ± PLD 30 mg/m^2 d 4	646	41 vs 44 (ORR)	10 vs 13	6.5 vs 9.3 (TTP) 6.5 vs 9.0 (PFS)
Chanan-Khan^Citation52	II	B-PLD + T	B 1.3 mg/m^2 d 1, 4, 15, 18 PLD 20 mg/m^2 d 1, 15 T 200 mg daily	17	42	23 (all CR)	10.9 (PFS)
Jakubowiak^Citation48	II	B-PLD + D	B 1.3 mg/m^2 d 1, 4, 8, 11 PLD 30 mg/m^2 d 4 D 40 mg d 1–4	18	22	33	N/A
Chari^Citation53	I/II	B-PLD + M	B 0.7–1.0 mg/m^2 d 1, 4, 8, 11 PLD 10–20 mg/m^2 d 1 M 5–10 mg/m^2 d 1	4	0	25	N/A

Abbreviations: B, bortezomib; D, dexamethasone; M, melphalan; PLD, pegylated liposomal doxorubicin; T, thalidomide; PR, partial response; CR, complete response; nCR, near complete response; ORR, overall response rate; PFS, progression-free survival; TTP, time to disease progression.

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