Melanoma

Metastatic melanoma refractory to checkpoint inhibitors is a challenging clinical scenario. We present the case of a patient who was refractory to standard ...

Little is known about the role of TVEC in this patient population, but other cases in addition to our own, suggest that TVEC may be a useful tool to overcome resistance to checkpoint inhibition [[6]](#references). This case allows us to hypothesize that not only the combination of, but also the sequencing of therapies in melanoma may be important by first “priming” and then later “unleashing” the immune system. [1c](#figure-anchor-354703)-d). The addition of TVEC to pembrolizumab did not improve progression free survival (PFS) or overall survival (OS) in a large phase III trial [[5]](#references). This was treated with SBRT (5 Gy over five fractions) followed by low-dose ipilimumab (3 mg/kg every 3 weeks for four doses). Both TVEC and SBRT have been postulated to be able to act synergistically with checkpoint inhibitors. We present a case of a heavily pretreated patient with metastatic melanoma who failed to respond to TVEC plus ipilimumab but responded dramatically to the combination of TVEC plus stereotactic body radiation therapy (SBRT) followed by ipilimumab. He had a complete response (CR) after SBRT for five months until he presented with a recurrent metastatic lesion on his back. Given his limited options, we recommended therapy with a combination of ipilimumab (3 mg/kg every 3 weeks) and TVEC. [[1-3]](#references). He was initially diagnosed in 2012 with a T2a (1.2mm, non-ulcerated) superficial spreading cutaneous melanoma on his back five years prior which was treated with local excision alone. While immunotherapy has dramatically changed the landscape of melanoma treatment, not all patients will respond to checkpoint inhibitors.