This study suggests that GI-irAE are different and less frequent with anti PD-1 than with anti CTLA-4.

Patients with cancer are at higher risk of severe coronavirus infectious disease 2019 (COVID-19), but the mechanisms underlying virus–host interactions during cancer therapies remain elusive. When comparing nasopharyngeal swabs from cancer and noncancer patients for RT-qPCR cycle thresholds measuring acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in 1063 patients (58% with cancer), we found that malignant disease favors the magnitude and duration of viral RNA shedding concomitant with prolonged serum elevations of type 1 IFN that anticorrelated with anti-RBD IgG antibodies. Cancer patients with a prolonged SARS-CoV-2 RNA detection exhibited the typical immunopathology of severe COVID-19 at the early phase of infection including circulation of immature neutrophils, depletion of nonconventional monocytes, and a general lymphopenia that, however, was accompanied by a rise in plasmablasts, activated follicular T-helper cells, and non-naive Granzyme B+FasL+, EomeshighTCF-1high, PD-1+CD8+ Tc1 cells. Virus-induced lymphopenia worsened cancer-associated lymphocyte loss, and low lymphocyte counts correlated with chronic SARS-CoV-2 RNA shedding, COVID-19 severity, and a higher risk of cancer-related death in the first and second surge of the pandemic. Lymphocyte loss correlated with significant changes in metabolites from the polyamine and biliary salt pathways as well as increased blood DNA from Enterobacteriaceae and Micrococcaceae gut family members in long-term viral carriers. We surmise that cancer therapies may exacerbate the paradoxical association between lymphopenia and COVID-19-related immunopathology, and that the prevention of COVID-19-induced lymphocyte loss may reduce cancer-associated death.

BackgroundImmune Checkpoint Inhibitors (ICI) have revolutionised the management of several cancers, enhancing the anti-tumoral immune response. However they are responsible for many Immune Related Adverse Effects (IRAE), and therefore most patients with Preexisting Autoimmune Diseases (PAD) have been excluded from clinical trials.ObjectivesThe aim of this study was to evaluate the safety and efficacy of ICI in patients with PAD.MethodsThree national expert networks, focusing respectively on skin cancers, thoracic cancers and inflammatory diseases participated in this study. All patients who received an ICI despite a PAD in clinical practice were included in this nationwide retrospective study.Results112 patients were included: 64 men (57.1%), median age 66.5. Most patients received an anti-PD1 or anti-PD-L1 drug (84.8%). Main cancer types were melanoma (n=66, 58.9%) and Non-Small Cell Lung Carcinoma (NSCLC) (n=40; 35.7%). Median follow-up was 8 months [0–52].Most frequent PAD were psoriasis and psoriatic arthritis (27.6%), rheumatoid arthritis (17.8%), inflammatory bowel disease (12.5%), spondyloarthritis (4.5%), lupus (6.3%), polymyalgia rheumatica and/or giant-cell arteritis (6.3%). 24 patients (21.6%) were receiving an immunosuppressive therapy (IS) at ICI initiation (including steroids in 15, sDMARD in 10 and rituximab in 1). 37 patients (33%) had an active disease.PAD flares were frequent (n=47; 42%) and 30.4% of them were severe (grade CTCAE 3–4). 26 patients (56.5%) received an IS treatment for a flare (22 received steroids and 7 a DMARD). Other IRAEs not related to the PAD occurred in 43 patients (38.4%), 41.5% were severe. 23 patients (56.1%) required an IS (including a DMARD in 4). 36 patients (32.1%) discontinued ICI temporarily or definitively because of a flare or an IRAE. One patient died due to an IRAE.Concerning the anti-tumoral response, the Overall Response Rate (ORR) was 48.3% for melanoma and 53.8% for NSCLC. The median Progression Free Survival (PFS) was 12.4 months for melanoma and 9.7 for NSCLC. Median overall survival (OS) was not reached in any group. PFS and OS were shorter in patients receiving an IS treatment at ICI initiation (p=0.007, figure 1A, and p=0.003, respectively). PFS and OS were longer in patients who experienced a PAD flare or other IRAE, but this gain was lost when an IS was used to treat the flare/IRAE (p=0.008, figure 1B, and p=0.01, respectively). Conversely, this gain was not impacted with ICI discontinuation.ConclusionsPAD flares and other IRAEs are frequent during ICI therapy and may be severe. The OS, ORR and PFS seem high in patients with PAD. The occurrence of a flare/IRAE is associated to a better outcome, gain lost when IS are used, while ICI discontinuation has no impact on PFS. Further prospective studies are needed to confirm our findings.Disclosure of InterestNone declared

No abstract