Systemic
immunotherapy with
PD-1 inhibitors is established in the treatment of metastatic
melanoma. However, up to 60% of patients do not show long-term benefit from a
PD-1 inhibitor monotherapy. Intralesional treatments with
immunomodulatory agents such as the oncolytic herpes virus
Talimogene Laherparepvec and
interleukin-2 (IL-2) have been successfully used in patients with
injectable metastases. Combination
therapy of systemic and local
immunotherapies is a promising treatment option in
melanoma patients. We describe a case series of nine patients with metastatic
melanoma and
injectable lesions who developed progressive disease under a
PD-1 inhibitor monotherapy. At the time of progressive disease, patients received intratumoral
IL-2 treatment in addition to
PD-1 inhibitor therapy. Three patients showed complete, three patients partial response and three patients progressive disease upon this combination
therapy. IHC stainings were performed from
metastases available at baseline (start of
PD-1 inhibitor) and under combination
therapy with
IL-2. IHC results revealed a significant increase of CD4+ and CD8+ T cells and a higher PD-1 expression in the inflammatory infiltrate of the tumor microenvironment in
metastases from patients with subsequent treatment response. All responding patients further showed a profound increase of the absolute eosinophil count (AEC) in the blood. Our case series supports the concept that patients with initial resistance to
PD-1 inhibitor therapy and
injectable lesions can profit from an additional intralesional
IL-2 therapy which was well tolerated. Response to this
therapy is accompanied by increase in AEC and a strong T cell-based inflammatory infiltrate.