Talimogene laherparepvec treatment to overcome loco-regional acquired resistance to immune checkpoint blockade in tumor stage IIIB–IV M1c melanoma patients

Abstract

Abstract Background Resistance 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. Methods All 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. Results Fourteen 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%. Conclusion T-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.