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Successful treatment with intralesional talimogene laherparepvec in two patients with immune checkpoint inhibitor-refractory, advanced-stage melanoma

Seremet, Teofilaa,c; Planken, Simona; Schwarze, Julia K.a; Jansen, Yaninaa; Vandeweerd, Lauraa; van den Begin, Robbeb; Tsechelidis, Ioannisd; Lienard, Daniellec; Del Marmol, Véroniquec; Neyns, Barta

doi: 10.1097/CMR.0000000000000501

Monoclonal antibodies that block the programmed death-1 (anti-PD-1) or cytotoxic T-lymphocyte antigen-4 (CTLA-4) immune checkpoint receptors (pembrolizumab, nivolumab, ipilimumab, or the combination of nivolumab with ipilimumab) are approved treatment option for patients with advanced melanoma. Over half of all patients are refractory to these immunotherapies and are in need of alternative or complementary treatment options. Talimogene laherparepvec (T-VEC) is a first-in-class intralesionally delivered oncolytic immunotherapy, which has proven efficacy in the treatment of advanced melanoma. A proportion of patients treated with T-VEC will benefit from an abscopal response of noninjected metastases indicative of a systemic antitumor immune response elicited by the intratumoral injections. At present it remains unknown whether the systemic antitumor responses elicited by T-VEC are nonredundant with immune-checkpoint blockade. Recent data on potential synergy between T-VEC and both PD-1 and CTLA-4 blockade suggest that the mechanism of action may be complementary. We report on the successful treatment with intralesional T-VEC of two female patients with locoregionally advanced BRAF V600 wild-type melanoma who previously progressed on anti-PD-1 and anti-CTLA-4 inhibitors.

aDepartment of Medical Oncology

bDepartment of Radiotherapy, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel (VUB)

cDepartment of Dermatology

dDepartment of Nuclear Medicine, Hôpital Erasme, Université Libre de Bruxelles (ULB), Brussels, Belgium

Correspondence to Teofila Seremet, MD, PhD, Department of Medical Oncology, UZ Brussel, Vrije Universiteit Brussel (VUB), Laarbeeklaan 101, 1090 Brussels, Belgium Tel: +32 2474 9478; fax: +32 2477 6210; e-mail:

Received January 26, 2018

Accepted August 10, 2018

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