Response and survival of metastatic melanoma patients treated with immune checkpoint inhibition for recurrent disease on adjuvant dendritic cell vaccination

Figures & data

Table 1. Patient baseline characteristics at the start of immune checkpoint inhibition

	PD-1 inhibition monotherapy after DC vaccination (n = 29)	Ipilimumab monotherapy after DC vaccination (n = 20)	Ipilimumab-nivolumab after DC vaccination (n = 8)
Age
Mean (range)	55 (37–74)	53 (24–69)	60 (43–78)
Sex
Male	17 (59%)	17 (85%)	8 (100%)
Female	12 (41%)	3 (15%)	0
Number of completed cycles of DC vaccination
0 (1 or 2 vaccines)	2 (7%)	0	2 (25%)
1	14 (48%)	3 (15%)	4 (50%)
2	6 (21%)	6 (30%)	1 (13%)
3	7 (24%)	11 (55%)	1 (13%)
Stage (AJCC 7^th ed.) at start of ICI
Unresectable stage III	5 (17%)	0	0
M1a	5 (17%)	3 (15%)	1 (13%)
M1b	8 (28%)	5 (25%)	0
M1c	11 (38%)	12 (60%)	7 (88%)
BRAF mutation
V600 mutation	16 (55%)	10 (50%)	6 (75%)
No V600 mutation	13 (45%)	5 (25%)	2 (25%)
Unknown	0	5 (25%)	0
Lactate dehydrogenase
≤ULN	26 (90%)	16 (80%)	3 (38%)
>ULN	3 (10%)	4 (20%)	5 (63%)
Cerebral metastases
Yes	0	4 (20%)	2 (25%)
No	24 (83%)	14 (70%)	6 (75%)
Unknown	5 (17%)	2 (10%)	0
Local treatment for cerebral metastases^a
No treatment	N/A	0	1 (50%)
Surgery	N/A	1 (25%)	0
Radiotherapy	N/A	3 (75%)	1 (50%)
Line of treatment
First	24 (83%)	10 (50%)	6 (75%)
Second	5 (17%)	10 (50%)	2 (25%)
Prior systemic treatment
None	24 (83%)	10 (50%)	6 (75%)
Dacarbazine	0	3 (15%)	0
PD-1 inhibition monotherapy	N/A	3 (15%)	0
BRAF/MEKi	2 (7%)	0	2 (25%)
BRAFi monotherapy	0	4 (20%)	0
Ipilimumab monotherapy	3 (10%)	N/A	0

^apercentage of patients having cerebral metastases.

Abbreviations: AJCC, American Joint Committee on Cancer; BRAF/MEKi, BRAF/MEK inhibition; BRAFi, BRAF inhibition; DC, dendritic cell; ICI, immune checkpoint inhibition; N/A, not applicable; ULN, upper limit of normal.

Figure 1. First- and second-line treatment in metastatic melanoma patients following recurrent disease on adjuvant dendritic cell vaccination. First- and second-line treatment is shown for the patients in the three different treatment groups. Three patients received first-line PD-1 inhibition monotherapy followed by second-line ipilimumab monotherapy, another three patients were treated with first-line ipilimumab monotherapy after which they received second-line PD-1 inhibition monotherapy. These six patients were analyzed in both the PD-1 inhibition monotherapy group (red) and the ipilimumab monotherapy group (blue). Therefore, the three treatment groups combined consisted of 57 analyzed patients

Abbreviations: ICI, immune checkpoint inhibition; ipi, ipilimumab; ipi-nivo, combined treatment with ipilimumab and nivolumab; mono, monotherapy.

Table 2. Clinical efficacy of immune checkpoint inhibition following dendritic cell vaccination

	PD-1 inhibition monotherapy after DC vaccination (n = 29)	Ipilimumab monotherapy after DC vaccination (n = 20)	Ipilimumab- nivolumab after DC vaccination (n = 8)
Response rate	15 (52%)	7 (35%)	6 (75%)
Disease control rate	21 (72%)	10 (50%)	6 (75%)
Best response on ICI
Complete response	7 (24%)	4 (20%)	2 (25%)
Partial response	8 (28%)	3 (15%)	4 (50%)
Stable disease	6 (21%)	3 (15%)	0
Progressive disease	8 (28%)	10 (50%)	2 (25%)
Median progression-free survival (months)	13.1	3.9	5.6
Median overall survival (months)	32.5	30.0	NR
Systemic treatment after progressive disease on ICI^a
No treatment for progressive disease	7 (41%)	4 (29%)	2 (50%)
Dacarbazine	0	1 (7%)	0
BRAF/MEKi	5 (29%)	1 (7%)	2 (50%)
BRAFi monotherapy	0	3 (21%)	0
(Re-introduction) Ipilimumab monotherapy	4 (24%)	0	0
(Re-introduction) PD-1 inhibition monotherapy	2 (12%)	7 (50%)	0
Ipilimumab-nivolumab	1 (6%)	1 (7%)	0
Treatment in a clinical trial	0	3 (21%)	0

^apercentage of the number of patients with progressive disease, patients may have been treated with multiple agents after progressive disease on immune checkpoint inhibition.

Abbreviations: BRAF/MEKi, BRAF/MEK inhibition; BRAFi, BRAF inhibitor; DC, dendritic cell; ICI, immune checkpoint inhibition; NR, not reached.

Figure 2. Progression-free and overall survival of patients treated with immune checkpoint inhibition following recurrence on adjuvant dendritic cell vaccination. Kaplan–Meier curves showing the progression-free and overall survival following PD-1 inhibition monotherapy (panels a, b); ipilimumab monotherapy (panels c, d) and ipilimumab-nivolumab (panels e, f) after recurrence on adjuvant DC vaccination. Survival data of first- and second-line therapy combined are shown in these panels

Abbreviation: mono, monotherapy.