Immunotherapy and Gastrointestinal Toxicities.

Gastrointestinal toxicities secondary to immune checkpoint inhibitors are very frequent. Because in some instances this can be severe or fatal, it is essential to be able to identify immune-related adverse events rapidly. Prompt initiation of systemic immunosuppression can improve outcomes. A biopsy is often necessary to confirm the diagnosis of immune-related adverse events. Moderate or severe irAEs need an interruption of ICI. After the resolution of the toxicities, the rechallenge of immune checkpoint inhibitors must be discussed case by case.

Humoral and cellular immunogenicity two months after SARS-CoV-2 messenger RNA vaccines in patients with cancer.

Little is known on the long-lasting humoral response and the T cell activation induced by SARS-CoV-2 mRNA vaccines in patients with cancer. The study assessed the efficacy of the SARS-CoV-2 mRNA vaccines through measuring the seroconversion rate at pre-specified time points and the effect on the T cell immunity in patients with cancers. The study included 131 adult patients with solid or hematological cancer, who received SARS-CoV-2 mRNA vaccines. 96.2% of them exhibited adequate antibody response to the SARS-CoV-2 mRNA vaccines 2 months after the booster dose. SARS-CoV-2 mRNA vaccines could induce T cell activation; however, this is more likely in patients who have a positive seroconversion (94%) compared with the patients who did not (50%). Further research into the clinical relevance of low antibodies titers and lack of T cell activity is required to set up an effective vaccination strategy within this group of patients.

SARS-CoV-2 Evolution among Oncological Population: In-Depth Virological Analysis of a Clinical Cohort.

BACKGROUND: Oncological patients have a higher risk of prolonged SARS-CoV-2 shedding, which, in turn, can lead to evolutionary mutations and emergence of novel viral variants. The aim of this study was to analyze biological samples of a cohort of oncological patients by deep sequencing to detect any significant viral mutations. METHODS: High-throughput sequencing was performed on selected samples from a SARS-CoV-2-positive oncological patient cohort. Analysis of variants and minority variants was performed using a validated bioinformatics pipeline. RESULTS: Among 54 oncological patients, we analyzed 12 samples of 6 patients, either serial nasopharyngeal swab samples or samples from the upper and lower respiratory tracts, by high-throughput sequencing. We identified amino acid changes D614G and P4715L as well as mutations at nucleotide positions 241 and 3037 in all samples. There were no other significant mutations, but we observed intra-host evolution in some minority variants, mainly in the ORF1ab gene. There was no significant mutation identified in the spike region and no minority variants common to several hosts. CONCLUSIONS: There was no major and rapid evolution of viral strains in this oncological patient cohort, but there was minority variant evolution, reflecting a dynamic pattern of quasi-species replication.

Immunogenicity of SARS-CoV-2 messenger RNA vaccines in patients with cancer.

Patients with cancer experience a higher burden of SARS-CoV-2 infection, disease severity, complications, and mortality, than the general population. SARS-CoV-2 mRNA vaccines are highly effective in the general population; however, few data are available on their efficacy in patients with cancer. Using a prospective cohort, we assessed the seroconversion rates and anti-SARS-CoV-2 spike protein antibody titers following the first and second dose of BNT162b2 and mRNA-1273 SARS-CoV-2 vaccines in patients with cancer in US and Europe from January to April 2021. Among 131 patients, most (94%) achieved seroconversion after receipt of two vaccine doses. Seroconversion rates and antibody titers in patients with hematological malignancy were significantly lower than those with solid tumors. None of the patients with history of anti-CD-20 antibody in the 6 months before vaccination developed antibody response. Antibody titers were highest for clinical surveillance or endocrine therapy groups and lowest for cytotoxic chemotherapy or monoclonal antibody groups.

[Immunotherapy with immune checkpoint inhibitor and skin toxicity]. / Immunothérapie par inhibiteurs de points de contrôle immunitaire et toxicité dermatologique.

Dermatologic toxicities appear to be the most prevalent immunotherapy related adverse effects, both with anti-PD-1 and anti-CTLA-4 agents, as well as with the newly developed anti-PD-L1. They occur in more than one-third of the patients treated with immune check point inhibitors, regardless of the cancer being treated. They mainly manifest in the form of self-limiting maculopapular rashes and pruritus. Early recognition and management are essential in order to mitigate the severity of the lesions. A multidisciplinary team is crucial for optimal management.

Les toxicités cutanées sont les effets indésirables les plus fréquents des inhibiteurs des points de contrôle immunitaire, que ce soit avec les anti-Programmed Cell Death 1, les anti-Cytotoxic T Lymphocyte Antigen-4 ou les nouveaux anti-Programmed Cell Death-Ligand 1. Ils surviennent chez plus d'un patient sur trois, et ce quel que soit le cancer traité. Ils se manifestent le plus souvent par un rash maculopapuleux limité au niveau du tronc et des membres et un prurit. Des toxidermies graves (syndromes de Lyell, de Stevens-Johnson ou d'hypersensibilité médicamenteuse) ainsi que des dermatoses autoimmunes (maladies bulleuses, lupus érythémateux disséminé) sont plus rares, mais leur reconnaissance et leur prise en charge précoces sont essentielles. Une évaluation multidisciplinaire est, dans ces cas, souvent indispensable pour une prise en charge optimale de la toxicité et ne pas prétériter la poursuite du traitement.