Management of partial and non-responding cutaneous squamous cell carcinoma.

Cutaneous squamous cell carcinoma (cSCC) and basal cell carcinoma are the most common types of skin cancer. For patients with locally advanced and metastatic cSCC, the programmed cell death 1 (PD-1) inhibitor cemiplimab is approved for systemic treatment. Despite this revolutionary immunomodulatory therapeutic approach, tumours may fail to respond either completely or partially. In addition to the previously established local treatment with radiotherapy or systemic treatment with chemotherapy and epidermal growth factor receptor inhibitors, ongoing trials are currently focussed on re-stimulating the antitumour immune response in patients with advanced cSCC refractory to PD-1 inhibitors. In this review, ongoing and recently finished trials with different therapeutic approaches will be discussed.

Checkpoint immunotherapy of cutaneous squamous cell carcinoma in patients suffering from chronic lymphocytic leukaemia: divergent outcomes in two men treated with PD-1 inhibitors.

Cutaneous squamous cell carcinoma (cSCC) numbers among the most common types of skin cancer and is known as one of the cancer entities with the highest mutational burden among all solid tumours. Due to the positive correlation between mutational burden and response rate to inhibitors of the programmed cell death 1 (PD-1), those inhibitors are considered promising candidates for the systemic therapy of cSCC. Recently, the PD-1 inhibitors pembrolizumab, nivolumab and cemiplimab demonstrated efficacy in the systemic treatment of locally advanced or metastatic cSCC leading to the approval of cemiplimab by the FDA (U.S. Food and Drug Administration) in 2018 and the EMA (European Medicines Agency) in 2019. Patients with haematological malignancies tend to develop skin cancers of high aggressiveness, enhanced cumulative recurrence rate and higher rates of metastases with subsequent death. Chronic lymphocytic leukaemia (CLL) is the most frequent type of leukaemia in the United States and Europe with the majority of patients older than 50 years of age. This neoplasm predominantly originates from B -cells leading to an impaired immune system of the patient. Although CLL is a B-cell malignancy, studies have also described the involvement of T cells in the pathogenesis and progression of the disease with contradictory findings on the effects of PD-1 inhibitors in CLL. Due to their underlying hematologic malignancy, these patients have commonly no access to PD-1 inhibitor trials for treatment of advanced cSCC. We report on two patients with locally advanced or metastatic cSCC. Both patients had been suffering from a CLL for many years without indication for treatment. Despite a potential immunosuppressive state of the patients due to their CLL, both were treated with the PD-1 inhibitor pembrolizumab resulting in different therapy outcomes.