Abstract
BackgroundResistance to immune checkpoint blockade and targeted therapy in melanoma patients is currently one of the major clinical challenges. With the approval of talimogene laherparepvec (T-VEC), oncolytic viruses are now in clinical practice for locally advanced or non-resectable melanoma. Here, we describe the usage of T-VEC in stage IVM1b-M1c melanoma patients, who achieved complete remission or stable disease upon systemic treatment but suffered from a loco-regional recurrence. To our knowledge, there are no case reports so far describing T-VEC as a means to overcome acquired resistance to immune checkpoint blockade or targeted therapy.MethodsAll melanoma patients in our department treated with T-VEC in the period of 2016–2018 were evaluated retrospectively. Data on clinicopathological characteristics, treatment response, and toxicity were analyzed.ResultsFourteen melanoma patients were treated with T-VEC in our center. Six patients (43%) received T-VEC first-line. In eight patients (57%), T-VEC followed a prior systemic therapy. Three patients with M1b stage and one patient with M1c stage melanoma were treated with T-VEC. These patients suffered from loco-regional progress, whilst distant metastases had regressed during prior systemic treatment. 64% of patients showed a benefit from therapy with T-VEC. The durable response rate was 36%.ConclusionT-VEC represents an effective and tolerable treatment option. This is true not only for loco-regionally advanced melanoma patients, but also for patients with stable or regressive systemic metastases who develop loco-regionally acquired resistance upon treatment with immune checkpoint blockade or targeted therapy. A sensible selection of suitable patients seems to be crucial.
Highlights
Over the last decade, targeted small-molecule inhibitors and checkpoint inhibitors have revolutionized the treatment of advanced melanoma
In eight patients (57%), therapy with talimogene laherparepvec (T-VEC) followed a prior systemic therapy (75% immunotherapy, 37.5% targeted therapy, 12.5% both, and adjuvant therapy with interferon was not considered as pretreatment)
These patients suffered from a locoregional progress, while distant metastases had been stable or regressive during prior systemic treatment
Summary
Over the last decade, targeted small-molecule inhibitors and checkpoint inhibitors have revolutionized the treatment of advanced melanoma. Talimogene laherparepvec (T-VEC) is the first oncolytic viral immunotherapy to be approved for patients with locally advanced or non-resectable melanoma (in 2015 in USA and in 2016 in Europe). T-VEC is designed to express human granulocytemacrophage colony-stimulating factor (GM-CSF) and US11 [2, 4] This cytokine stimulus synergistically enhances the ongoing immune activation, promoting a local and systemic anti-tumor immune response, even at non-injected lesions and distant sites [5, 6]. Conclusion T-VEC represents an effective and tolerable treatment option This is true for loco-regionally advanced melanoma patients, and for patients with stable or regressive systemic metastases who develop loco-regionally acquired resistance upon treatment with immune checkpoint blockade or targeted therapy. A sensible selection of suitable patients seems to be crucial
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