Improved survival over time with immunotherapy in locally advanced and metastatic cutaneous squamous cell carcinomas.

PURPOSE: Cutaneous squamous cell carcinoma (cSCC) is the second most common cancer in white-skinned populations. There is little information on the epidemiology of cSCC, and even less on advanced cases (acSCC). Therefore, we analyzed acSCC patients to describe their characteristics, management, and outcomes over time. METHODS: A single-center retrospective study was conducted over a period of 5 years, including all patients who started systemic therapy for acSCC. The patient characteristics, cSCC management, response to therapy, and survival were recorded. Patients were stratified into equal chronological periods (periods 1 and 2). A subgroup analysis was performed to compare patients who received immunotherapy (group 1) with those who did not (group 2). RESULTS: The study included 127 patients, and patient numbers increased by an average of 19.7% per year. Most patients were male (88/127), elderly (mean 81.6 years), with comorbidities, and 27.6% were immunocompromised. The median overall survival (OS) was higher in period 2 (20 months) than in period 1 (10 months) (hazard ratio [95% confidence interval] = 0.62 [0.39; 0.98], p = 0.04). The risk of progression increased with age and immunosuppression. Of the 64 patients who received second-line therapy, 38 had immunotherapy (group 1) and 26 received other therapies (group 2). Immunotherapy reduced mortality and progression by 71% (p = 0.004) and 67% (p = 0.002), respectively. CONCLUSIONS: Patients with acSCC are usually very frail and elderly. OS increased over time, with a twofold improvement between periods 1 and 2, whereas progression-free survival (PFS) did not increase. Access to immunotherapy reduced mortality in a majority of patients in period 2. Immunosuppression and advanced age were associated with lower PFS.

Proliferative Tumor-Infiltrating Lymphocytes' Abundance within the Microenvironment Impacts Clinical Outcome in Cutaneous B-Cell Lymphomas.

Primary cutaneous large B-cell lymphoma, leg-type (PCLBCL-LT) is the most aggressive primary cutaneous B-cell lymphoma (PCBCL). Tumor microenvironment has a crucial role in tumor development, and tumor-infiltrating lymphocytes (TILs) can be targeted by immunotherapies. We characterized TILs in 20 PCBCLs to identify the tumor microenvironment features associated with clinical outcomes. We developed a seven‒multiplex immunofluorescence panel using Opal staining and image analysis using HALO software. In PCLBCL-LT, TILs were sparsely intermingled within tumor infiltrate in contrast to those in indolent PCBCL where TILs were scattered around tumor nodule edges with variable tumor infiltration. In PCLBCL-LT, TILs were composed of CD8 and CD4, whereas CD4 was predominant in indolent PCBCL. Proliferative TILs (CD3+Ki-67+ cells) were more abundant in PCLBCL-LT (P = 0.0036) than in indolent PCBCL. In PCLBCL-LT, proliferative TILs' abundance tended to be associated with better progression-free survival. These data were confirmed in a second independent cohort of 23 cases showing that proliferative TILs were more abundant in PCLBCL-LT (P = 0.0205) and that in PCLBCL-LT, high CD3+Ki-67+ cell density was associated with better progression-free survival (P = 0.002). These distinct TILs composition and distribution among PCBCL suggest that proliferative T lymphocytes represent a good prognostic factor in PCLBCL-LT and that stimulating their functions may represent a therapeutic approach.

A High Programmed Cell Death Protein 1 Hormone Receptor Score on Skin Biopsy is Associated with Sézary Syndrome Diagnosis: A Study of 91 Patients with Erythroderma.

Erythroderma is challenging to diagnose. The aim of this single-centre retrospective study was to identify factors that can be used to improve the diagnosis of erythroderma. Among 91 patients with erythroderma, 21 were diagnosed with eczema, 17 with psoriasis, 20 with drug-induced erythroderma, 13 with erythrodermic mycosis fungoides and 20 with Sézary syndrome. Nail alterations, ear involvement, and severe scaling were significantly associated with psoriasis (p = 0.044). Fever and hypereosinophilia were associated with drug-induced erythroderma. Expression of programmed cell death protein 1 was observed in all skin biopsies. However, with Sézary syndrome, programmed cell death protein 1 expression was significantly higher than with other aetiologies. A programmed cell death protein 1 hormone receptor score (H-score) >50 was associated with Sézary syndrome (p < 0.001, sensitivity 75%, specificity 92%) as well as CXCL13 expression (p < 0.044). CD7 loss was more frequent with erythrodermic mycosis fungoides and Sézary syndrome (p = 0.022). This study reports the importance of programmed cell death protein 1 expression for the differential diagnosis of Sézary syndrome and other aetiologies, including erythrodermic mycosis fungoides.

Risk Factors of Midterm Mortality After Aortic Valve Replacement for Severe Calcified Tricuspid Aortic Valve Stenosis: A retrospective analysis of Perioperative Events Assessment in Adult Cardiac surgery (PESSAC) Registry.

OBJECTIVE: The European System for Cardiac Operative Risk Evaluation II (EuroSCORE II) initially developed for predicting early postoperative mortality of all types of cardiac surgery, is less able to predict, more specifically, long-term outcomes after aortic valve replacement (AVR). The study authors here evaluated the risk factors for three-year mortality after isolated aortic valve replacement (AVR) for severe calcified tricuspid aortic valve stenosis and compared them with EuroSCORE II to predict long-term outcomes. DESIGN: A retrospective study. SETTING: A university teaching hospital. PARTICIPANTS: This study included 1,101 adults who underwent isolated AVR for severe calcified tricuspid aortic valve stenosis between September 2010 to June 2015. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary endpoint was that of three-year all-cause mortality after AVR. By three years, 168 patients (15.3%) had died. Risk factors for all-cause mortality were: male gender (odds ratio [OR] = 1.78; 95% confidence interval [CI] = 1.21-2.62; p < 0.01), peripheral arterial disease (OR = 1.77; 95% CI = 1.08-2.92; p = 0.03), age (OR = 1.06 per year increase; 95% CI =1.04-1.09; p < 0.01), pulmonary artery systolic pressure (OR = 1.02 per mmHg increase; 95% CI = 1.01-1.03; p < 0.01), platelet count (OR = 1.003 per G/L increase; 95% CI = 1.000-1.005; p = 0.04), and valve area (OR = 0.97 per cm²/m² increase; 95% CI= 0.95-0.99; p < 0.01). The area under the receiver operating characteristic curves were 0.67 (95% CI = 0.60-0.75) and 0.60 (95% CI = 0.56-0.65) for the authors' logistic regression model and EuroSCORE II, respectively (p = 0.11). CONCLUSIONS: The study authors identified six independent risk factors for three-year mortality after isolated AVR. The logistic regression model had relatively modest predictive performance for three-year mortality.

Real-World Survival in Patients with Metastatic Melanoma after Discontinuation of Anti-PD-1 Immunotherapy for Objective Response or Adverse Effects: A Retrospective Study.

OBJECTIVE: Anti-PD-1 has dramatically improved the survival of patients with advanced melanoma. However, there is a lack of data on maintenance of the response after treatment discontinuation. We aimed to evaluate the progression-free survival (PFS) of patients with metastatic melanoma after anti-PD-1 interruption for objective response (OR) or limiting toxicity during clinical trials. METHODS: All patients with advanced melanoma who stopped single-agent anti-PD-1 antibodies for objective response or toxicity were included between April 2014 and January 2019 in our institution (data cut-off, September 10th, 2019). Clinical and biological factors associated with relapse were studied. RESULTS: The median follow-up after introduction of treatment was 36.5 months [4.6-62.4], and the median follow-up after discontinuation of treatment was 15.7 months (2.5-45.1). Out of 65 patients, 28 patients stopped immunotherapy for limiting adverse effects (AEs) (43.1%), 25 for complete response (CR) (38.4%), and 12 for partial response (PR) or long-term stable disease (SD) (18.5%). Twelve patients relapsed (18.5%) after a median time of 9 months [1.9-40.9 months]. Seven relapsed after discontinuation for AEs, 3 after discontinuation for CR, and 2 after discontinuation for PR/SD. The median PFS after therapy discontinuation was not reached. No statistical association was found between recurrence and age, sex, increased LDH, BRAF status, presence of brain metastases, previous treatments, radiotherapy, or time on anti-PD-1 treatment. CONCLUSION: This cohort shows a global recurrence rate of 18.5% and confirms a long-lasting response after anti-PD-1 cessation regardless of the cause of discontinuation.

Real world safety outcomes using cemiplimab for cutaneous squamous cell carcinoma.

INTRODUCTION: Locally advanced or metastatic cutaneous squamous cell carcinoma (cSCC) mostly affects older and frail patients. Cemiplimab is an anti-PD1 antibody used in this indication since its approval by the FDA and the EMA in 2019 after encouraging results from phase II trials. We aimed to evaluate cemiplimab safety in patients from daily practice. METHODS: Retrospective and monocentric study including all patients who received at least one infusion of cemiplimab between August 2018 and September 2019. Adverse effects (AEs), treatment interruption, and efficacy were recorded (data cut-off, November 1st 2020). RESULTS: Twenty-two patients were included, median age was 83 [55-93], 73% were Eastern Cooperative Oncology Group (ECOG) 0 or 1, 36% were immune compromised. After a median time on treatment of six months [0.7-22], seventeen patients (77%) experienced 24 AEs, comprising 45% serious AEs (SAEs) grade ≥ 3 and one SAE grade 5 (myositis). Patients who presented SAEs were all >65 years old. Nine patients (41%) definitively discontinued treatment due to AEs. Seventeen patients were evaluable, after a median follow-up of eleven months [1-22], 32% had an objective response (2 complete and 5 partial responses), 47% had controlled disease and 35% experienced progression. CONCLUSIONS: In our cohort, safety seemed to be worse than in phase II trial with more treatment discontinuations due to cemiplimab toxicity, probably reflecting the distinct demographic and medical characteristics of patients in daily care.