Local adjuvant treatment with low-dose CpG-B offers durable protection against disease recurrence in clinical stage I–II melanoma: Data from two randomized phase II trials

Bas D. Koster, Mari F.C.M. Van Den Hout, Berbel J.R. Sluijter, Barbara G. Molenkamp, Ronald J.C.L.M. Vuylsteke, Arnold Baars, Paul A.M. Van Leeuwen, Rik J. Scheper, M. Petrousjka van den Tol, Alfons J.M. Van Den Eertwegh, Tanja D. De Gruijl

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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.

Original languageEnglish
Pages (from-to)5679-5686
Number of pages8
JournalClinical Cancer Research
Issue number19
Publication statusPublished - 1 Oct 2017

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