ABSTRACT
Cemiplimab, a human monoclonal antibody directed against PD-1, has provided more options in the treatment of locally advanced or metastatic cutaneous squamous-cell carcinoma at an unresectable state. Immune checkpoint inhibitors can induce several unfavorable reactions generally referred to as immune-related adverse effects. Cytokine-release syndrome is an immune-related adverse event that is infrequent and not well known. Diagnosis is difficult because of the unspecific symptoms (e.g., fever, hypotension) but it can also be life threatening. The authors report the case of a 62-year-old treated by cemiplimab for a cutaneous squamous-cell carcinoma of the diaper fold with iliac and inguinal lymph node extension. He presented with severe cytokine-release syndrome, concluding with the discontinuation of cemiplimab.
Immunotherapy has become an increasingly important part of cancer treatment. This treatment has many side effects, mainly linked with immune system activation. Cytokine-release syndrome is one of the rare complications; it causes hyperthermia, hypotension and biological inflammation. Diagnosis of this syndrome is critical, as it can be life threatening. Diagnosis and early management, including stopping immunotherapy and administering corticosteroids and, in some cases, anti-IL- 6, leads to a favorable outcome in the majority of cases. The authors report the second case of cytokine-release syndrome after cemiplimab infusion used in the first-line treatment of cutaneous unresectable squamous-cell carcinoma.
Subject(s)
Carcinoma, Squamous Cell , Skin Neoplasms , Male , Humans , Middle Aged , Antibodies, Monoclonal, Humanized/adverse effects , Skin Neoplasms/pathology , Carcinoma, Squamous Cell/pathology , CytokinesABSTRACT
Background: Although effective mRNA vaccines for SARS-CoV-2 infection have been deployed worldwide, their interchangeability could facilitate the scale-up of vaccination programs. The objective of the trial was to assess whether the immune response induced by a heterologous SARS-CoV-2 mRNA primo vaccination is non-inferior to that of a homologous mRNA vaccination. Methods: We conducted a multicenter, randomized, open-label trial in adults 18 years of age and older who received a first dose of SARS-CoV-2 mRNA vaccine. Participants were randomly assigned in a 1:1 ratio to receive a second dose of BNT162b2 or mRNA-1273, 28 to 49 days after the first dose. Randomization was stratified on the vaccine received at the first vaccination. The primary endpoint was the anti-spike IgG antibodies titer measured 28 days after the second vaccine dose. This study is registered with ClinicalTrials.gov, Trial, NCT04900467. Findings: Of the 414 randomized participants recruited from May 28 to July 2, 2021, 390 were included in the per protocol analysis: 94 participants in group 1 (BNT162b2/BNT162b2), 96 in group 2 (BNT162b2/mRNA-1273), 97 in group 3 (mRNA-1273/mRNA-1273), and 103 in group 4 (mRNA-1273/BNT162b2). The geometric mean titers ratios of anti-spike IgG antibodies for each heterologous regimen relative to the corresponding homologous regimen were 1·37 (two-sided 95% CI, 1·10 to 1·72) in the groups 1 and 2 and 0·67 (two-sided 95% CI, 0·55 to 0·82) in the groups 3 and 4. Levels of neutralizing antibodies to the main circulating SARS-Cov-2 viral strains were higher with the vaccine regimen containing mRNA-1273. Participants who received mRNA-1273 as a second dose experienced a higher rate of local adverse reactions and general symptoms than those who received BNT162b2 (p < 0·0001). Interpretation: The two SARS-CoV-2 mRNA vaccines could be used with flexibility for the second dose of COVID-19 primo vaccination. Tolerance remains good regardless of vaccine sequence although mRNA-1273 was more reactogenic. Funding: French Ministries of Solidarity and Health and Research. BNT162b2 was provided by Pfizer/BioNTech. mRNA-1273 was provided by Moderna.
ABSTRACT
BACKGROUND: In recent years, the clinical use of interferon gamma release assays (IGRAs) has increased exponentially, while their indications remain controversial given difficulties in interpretation. Four indications were recommended by the French National Authority for Health (HAS) in 2006. We evaluated the utilization of the QuantiFERON-TB Gold In-Tube (QFT-IT) test over a 1-y period in a French university hospital and the impact of IGRA results in particular. METHODS: The QFT-IT tests requested in 2009 were analysed retrospectively, excluding those from the Occupational Health Department, the Regional Tuberculosis Centre, and rheumatology consultations for which the indications were clearly defined. RESULTS: Three hundred and sixty QFT-IT tests were analysed. The interpretation was frequently problematic given the inclusion of a significant proportion of patients over 80 y of age (11%), immunocompromised patients (43%), and patients with a known history of tuberculosis (6%). The indications failed to comply with HAS recommendations in 42% of cases (151/360), i.e. 14% of all QFT-IT tests in 2009. Thirty-seven percent of request forms were related to suspected pulmonary tuberculosis. In the case of a positive QFT-IT test, the clinical decision-making was changed in 58% of cases when the indications met the HAS recommendations, compared with only 16% if they did not (p < 0.005). CONCLUSION: When the indications do not meet the health authority recommendations, the diagnostic value of the IGRA remains limited.
