TY - JOUR
T1 - Local Adjuvant Treatment with Low-Dose CpG-B Offers Durable Protection against Disease Recurrence in Clinical Stage I-II Melanoma
T2 - Data from Two Randomized Phase II Trials
AU - Koster, Bas D.
AU - van den Hout, Mari F. C. M.
AU - Sluijter, Berbel J. R.
AU - Molenkamp, Barbara G.
AU - Vuylsteke, Ronald J. C. L. M.
AU - Baars, Arnold
AU - van Leeuwen, Paul A. M.
AU - Scheper, Rik J.
AU - van den Tol, M. Petrousjka
AU - van den Eertwegh, Alfons J. M.
AU - de Gruijl, Tanja D.
PY - 2017/10/1
Y1 - 2017/10/1
N2 - Purpose: Although risk of recurrence after surgical removal of clinical stage I-II melanoma is considerable, there is no adjuvant therapy with proven efficacy. Here, we provide clinical evidence that a local conditioning regimen, aimed at immunologic arming of the tumor-draining lymph nodes, may provide durable protection against disease recurrence (median follow-up, 88.8 months).Experimental Design: In two randomized phase II trials, patients, diagnosed with stage I-II melanoma after excision of the primary tumor, received local injections at the primary tumor excision site within 7 days preceding re-excision and sentinel lymph node (SLN) biopsy of either a saline placebo (n = 22) or low-dose CpG type B (CpG-B) with (n = 9) or without (n = 21) low-dose GM-CSF.Results: CpG-B treatment was shown to be safe, to boost locoregional and systemic immunity, to be associated with lower rates of tumor-involved SLN (10% vs. 36% in controls, P = 0.04), and, at a median follow-up of 88.8 months, to profoundly improve recurrence-free survival (P = 0.008), even for patients with histologically confirmed (i.e., pathologic) stage I-II disease (P = 0.02).Conclusions: Potentially offering durable protection, local low-dose CpG-B administration in early-stage melanoma provides an adjuvant treatment option for a large group of patients currently going untreated despite being at considerable risk for disease recurrence. Once validated in a larger randomized phase III trial, this nontoxic immunopotentiating regimen may prove clinically transformative. (C) 2017 AACR.
AB - Purpose: Although risk of recurrence after surgical removal of clinical stage I-II melanoma is considerable, there is no adjuvant therapy with proven efficacy. Here, we provide clinical evidence that a local conditioning regimen, aimed at immunologic arming of the tumor-draining lymph nodes, may provide durable protection against disease recurrence (median follow-up, 88.8 months).Experimental Design: In two randomized phase II trials, patients, diagnosed with stage I-II melanoma after excision of the primary tumor, received local injections at the primary tumor excision site within 7 days preceding re-excision and sentinel lymph node (SLN) biopsy of either a saline placebo (n = 22) or low-dose CpG type B (CpG-B) with (n = 9) or without (n = 21) low-dose GM-CSF.Results: CpG-B treatment was shown to be safe, to boost locoregional and systemic immunity, to be associated with lower rates of tumor-involved SLN (10% vs. 36% in controls, P = 0.04), and, at a median follow-up of 88.8 months, to profoundly improve recurrence-free survival (P = 0.008), even for patients with histologically confirmed (i.e., pathologic) stage I-II disease (P = 0.02).Conclusions: Potentially offering durable protection, local low-dose CpG-B administration in early-stage melanoma provides an adjuvant treatment option for a large group of patients currently going untreated despite being at considerable risk for disease recurrence. Once validated in a larger randomized phase III trial, this nontoxic immunopotentiating regimen may prove clinically transformative. (C) 2017 AACR.
KW - SENTINEL LYMPH-NODE
KW - T-CELL REACTIVITY
KW - DENDRITIC CELLS
KW - CD8(+) T
KW - SURVIVAL
KW - ACTIVATION
KW - VACCINATION
KW - ANTIGEN
U2 - 10.1158/1078-0432.CCR-17-0944
DO - 10.1158/1078-0432.CCR-17-0944
M3 - Article
C2 - 28972083
SN - 1078-0432
VL - 23
SP - 5679
EP - 5686
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 19
ER -