Successful combination therapy of systemic checkpoint inhibitors and intralesional interleukin-2 in patients with metastatic melanoma with primary therapeutic resistance to checkpoint inhibitors alone.

Successful combination therapy of systemic checkpoint inhibitors and intralesional interleukin-2 in patients with metastatic melanoma with primary therapeutic resistance to checkpoint inhibitors alone.

Publication date: Aug 17, 2019

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.

Rafei-Shamsabadi, D., Lehr, S., von Bubnoff, D., and Meiss, F. Successful combination therapy of systemic checkpoint inhibitors and intralesional interleukin-2 in patients with metastatic melanoma with primary therapeutic resistance to checkpoint inhibitors alone. 23804. 2019 Cancer Immunol Immunother.

Concepts Keywords
AEC Metastases
Blood Melanoma
CD4 Immunotherapy
CD8 Immunotherapies
Combination Therapy Medicine
Eosinophil Clinical medicine
Immunomodulatory Cancer treatments
Immunotherapies Health
Immunotherapy Immune system
Inhibitor Melanoma
Interleukin 2 RTT
Melanoma Immunotherapy
Metastases Checkpoint inhibitor
Monotherapy Pembrolizumab
Progressive

Semantics

Type Source Name
disease MESH tumor
gene UNIPROT CD4
disease MESH metastases
drug DRUGBANK Talimogene laherparepvec
gene UNIPROT RPL17
pathway BSID Melanoma
disease DOID melanoma
disease MESH melanoma
gene UNIPROT IL2

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