C. Templier

Ipilimumab in anti-PD1 refractory metastatic melanoma: a report of eight cases.

Targeted therapy and immunotherapy in metastatic melanoma have led to a marked improvement in patients’ survival and their quality of life. Although there are data on anti-programmed-death-receptor-1 (anti-PD1) after ipilimumab, only few data are available on ipilimumab following anti-PD1 as the first-line treatment. The aim of our study was to evaluate tolerance and survival of patients treated with ipilimumab as the second-line immunotherapy among metastatic melanoma patients following anti-PD1 treatment. Retrospective and descriptive epidemiological studies were carried out at the Dermatology Department of the University Hospital of Lille. We describe a case series of patients treated with ipilimumab after anti-PD1 failure for metastatic melanomas. For each patient, we assessed disease extension since ipilimumab introduction using RECIST 1.1. The time between ipilimumab introduction and other systemic treatment and overall survival (between ipilimumab introduction and last patient visit) was assessed. The effect of ipilimumab after anti-PD1 treatment was evaluated in eight patients. Four patients responded to ipilimumab: three showed a complete response and one showed a partial response. For these patients, the time period between the first ipilimumab injection and another systemic treatment ranged from 209 to 391 days and the overall survival ranged from 314 to 581 days. One patient showed grade 3 chorioretinitis, an unusual toxicity with ipilimumab or anti-PD1 to our knowledge. We have described the efficacy of ipilimumab following anti-PD1 in metastatic melanoma in eight patients. Several comparative studies are still in progress, and their results will be important to develop an optimal therapeutic strategy for our patients.

Pembrolizumab-induced pneumonitis

Immune checkpoint inhibitors are promising new therapies for advanced cancers. In particular, antibodies against programmed cell death 1 (PD-1), such as nivolumab and pembrolizumab, increase anti-tumour T cell responses by blocking the interaction between PD-1 on T cells and its ligand PD-L1 on cancer cells [1]. Enhanced T-cell responses resulting from checkpoint inhibition can lead to an unusual spectrum of side effects called immune-related adverse events, which involve numerous organs, particularly the skin, liver, and gastrointestinal and endocrine systems [2–11]. Pneumonitis is a potentially lethal side effect of immune checkpoint inhibition, occurring in 1–5% of patients enrolled in trials [2–11]. However, little is known about the clinical and radiological features of checkpoint inhibitor-induced lung disease. Here, we report three cases of pembrolizumab-induced acute interstitial lung disease (ILD). The medical data of the patients presented below were collected in accordance with French regulations, none of which was opposed to their uses. Three cases of pembrolizumab-induced pneumonitis are described, two being consistent with organising pneumonia http://ow.ly/Dvhc308QI39

BRAF inhibitor discontinuation and rechallenge in advanced melanoma patients with a complete initial treatment response

BRAF inhibitors (BRAFi), a targeted therapy, are used to treat metastatic late-stage melanomas harbouring the BRAF-V600 mutation (found in about 50% of melanomas). The targeted therapy is generally maintained until tumour progression or major toxicity occurs, although responses are often limited in time. It is unknown whether melanoma patients achieving a complete response with targeted therapy can safely discontinue treatment. We retrospectively observed the clinical course of patients with metastatic melanoma who discontinued BRAFi therapy after achieving a complete response and those with an incomplete response combined with surgical removal of the remaining tumours. We also evaluated the effectiveness of BRAFi in these patients after recurrence. In 11 patients, the best response was diagnosed after a median BRAFi treatment duration of 105 (29–341) days. The median follow-up after BRAFi initiation was 769 (435–1765) days. Recurrence was observed in all 11 patients (100%), median: 82 (27–322) days. Five patients achieved a complete response, with a median progression-free survival after cessation of 136.5 (34–322) days versus 82 (27–144) days for six patients with an incomplete response combined with surgical removal of remaining tumours. Baseline characteristics and time to best response and to discontinuation did not influence the rate of relapse. Subsequently, eight patients were rechallenged with a BRAFi. The median progression-free survival time after BRAFi rechallenge was 222.5 (15–425) days. The three remaining patients received treatments other than BRAFi. Our findings may be valuable with respect to ongoing clinical trials of combinations of targeted therapies and immunomodulatory antibodies.

Occurrence of vismodegib-induced cramps in the treatment of basal cell carcinoma: a prospective study in 30 patients

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