VTD-melphalan is well tolerated and results in very high rates of stringent CR and MRD-negative status in multiple myeloma

Figures & data

Table 1 Patient characteristics

Variable	Level	n	%
Tandem or single	Single	47	47.0
	Tandem	53	53.0
Early salvage	Salvage	36	36.0
	Early	64	64.0
Previous transplant	No	80	80.0
	Yes	20	20.0
Cytogenetics	Chromosome 1 abnormalities	18	18.0
	High risk	24	24.0
	Standard risk	76	76.0
Durie-Salmon staging and subclassification at diagnosis	I	16	16.3
	II	12	12.2
	III	70	71.4
	Missing	2	–
ISS	I	30	33.3
	II	34	37.8
	III	26	28.9
	Missing	10	–
R-ISS	I	18	25.7
	II	41	58.6
	III	11	15.7
	Missing	30	–
Pre-transplant MRD status	Negative	11	11.6
	Positive	84	88.4
	Missing	5	–
Pre-transplant response	1: sCR	1	1.0
	2: CR	11	11.0
	3: VGPR/nCR	11	11.0
	4: PR	56	56.0
	5: SD	19	19.0
	6: PD	1	1.0
	8: Never treated	1	1.0
Post-transplant MRD status	Negative	82	85.4
	Positive	14	14.6
	Missing	4	–
Post-transplant response	1: sCR	55	56.1
	2: CR	20	20.4
	3: VGPR/nCR	10	10.2
	4: PR	12	12.2
	5: SD	1	1.0
	Missing	2	–
		Median	Range
Age at first transplant		60.5	37.0–80.0
Creatinine at diagnosis (mg/dL)		1.0	0.5–19.0
Albumin at diagnosis (g/dL)		3.9	0.3–5.1
LDH at diagnosis (U/L)		1.7	0.8–4.2
Length of follow-up (months)		16.2	1.5–35.0

Abbreviations: CI, confidence interval; ISS, International Staging System; LDH, lactate dehydrogenase; MRD, minimal residual disease; nCR, near complete response; R-ISS, revised International Staging System; sCR, stringent complete remission; SD, stable disease; VGPR, very good partial response; CR, complete remission; PR, partial remission; PD, progressive disease.

Table 2 Rate of maximum grade 3–5 and overall toxicity per transplant

	Grade			Overall
		n	%	n	%
Blood and lymphatic system disorders	3	4	2.6	152	99.3
	4	148	96.7
Metabolism and nutrition disorders	3	79	51.6	93	60.8
	4	14	9.2
Other hepatobiliary disorders	3	6	3.9	7	4.6
	4	1	0.7
Gastrointestinal disorders	3	53	34.6	58	37.9
	4	5	3.3
Infections and infestations	3	48	31.4	56	36.6
	4	7	4.6
	5	1	0.7
Respiratory, thoracic and mediastinal disorders	3	12	7.8	13	8.5
	4	1	0.7
Cardiac disorders	3	10	6.5	12	7.8
	4	2	1.3
General disorders and administration site conditions	3	22	14.4	24	15.7
	4	2	1.3
Vascular disorders	3	17	11.1	18	11.8
	4	1	0.7
Other bleeding complication	3	2	1.3	3	2
	4	1	0.7
Nervous system disorders	3	13	8.5	15	9.8
	4	2	1.3
Other musculoskeletal and connective tissue disorders	3	6	3.9	6	3.9
Psychiatric disorders	3	8	5.2	8	5.2
Other skin and subcutaneous tissue disorders	3	2	1.3	3	2
	4	1	0.7
Immune system disorders – engraftment syndrome	3	10	6.5	11	7.2
	4	1	0.7
Renal and urinary disorders	3	10	6.5	11	7.2
	4	1	0.7
Eye disorders	3	1	0.7	1	0.7

Table 3 Univariate association between prognostic factors and best response within 180 days post-transplant

Covariate	Level	n	Odds of having sCR or CR
			OR	95% CI		OR P-value	Overall P-value
Age (years)	65+	36	0.55	0.21	1.41	0.21	0.21
	<65	62	Ref	–	–	–
Cytogenetics	High risk	24	1.73	0.52	5.70	0.37	0.37
	Standard Risk	74	Ref	–	–	–
Previous transplant	No	78	2.80	0.97	8.06	0.06	0.06
	Yes	20	Ref	–	–	–
Early or salvage	Early	63	2.47	0.95	6.40	0.06	0.06
	Salvage	35	Ref	–	–	–
Durie-Salmon staging and subclassification at diagnosis	II	12	0.51	0.10	2.57	0.41	0.22
	III	69	1.57	0.43	5.71	0.50
	I	15	Ref	–	–	–
ISS	II	32	0.71	0.20	2.56	0.61	0.65
	III	26	0.54	0.15	1.98	0.35
	I	30	Ref	–	–	–
R-ISS	II	40	0.18	0.02	1.50	0.11	0.19
	III	11	0.59	0.03	10.48	0.72
	I	18	Ref	–	–	–
Tandem or single	Tandem	51	1.98	0.76	5.14	0.16	0.16
	Single	47	Ref	–	–	–
Creatinine at diagnosis	Units =1	90	0.94	0.82	1.09	0.40	0.40
Albumin at diagnosis	Units =1	90	1.21	0.66	2.22	0.54	0.54
LDH at diagnosis	Units =1	64	2.48	0.57	10.89	0.23	0.23

Abbreviations: CI, confidence interval; LDH, lactate dehydrogenase; OR, odds ratio; ISS, International Staging System; CR, complete response; R-ISS, revised International Staging System; sCR, stringent complete response; Ref, reference.

Table 4 Univariate association between prognostic factors and MRD status within 180-days post-transplant

Covariate	Level	n	Odds of MRD positivity
			OR	95% CI		OR P-value	Overall P-value
Age (years)	65+	36	1.83	0.58	5.72	0.30	0.30
	<65	60	Ref	–	–	–
Cytogenetics	High risk	24	0.79	0.20	3.12	0.74	0.74
	Standard risk	72	Ref	–	–	–
Previous transplant	No	77	0.56	0.15	2.03	0.38	0.38
	Yes	19	Ref	–	–	–
Early or salvage	Early	62	0.35	0.11	1.11	0.07	0.07
	Salvage	34	Ref	–	–	–
Durie-Salmon staging and subclassification at diagnosis	II	11	0.61	0.09	4.14	0.61	0.25
	III	68	0.32	0.08	1.26	0.10
	I	15	Ref	–	–	–
ISS	II	31	0.13	0.01	1.14	0.07	0.17
	III	26	0.91	0.24	3.44	0.89
	I	29	Ref	–	–	–
R-ISS	II	39	2.91	0.32	26.24	0.34	0.59
	III	11	1.60	0.09	28.56	0.75
	I	17	Ref	–	–	–
Tandem or single	Tandem	51	0.86	0.28	2.68	0.80	0.80
	Single	45	Ref	–	–	–
Creatinine at diagnosis	Units =1	88	0.94	0.72	1.23	0.67	0.67
Albumin at diagnosis	Units =1	88	0.75	0.36	1.53	0.42	0.42
LDH at diagnosis	Units =1	62	0.41	0.05	3.14	0.39	0.39

Abbreviations: CI, confidence interval; LDH, lactate dehydrogenase; MRD, minimal residual disease; OR, odds ratio; ISS, International Staging System; R-ISS, revised International Staging System; Ref, reference.