VIH et cancer : mise au point en 2020

International audienceThe HIV infection remains a serious public health concern in France and around the world. Cancers are frequent among people living with HIV (PLWH) and have become the leading cause of mortality among this population in France. Certain non-AIDS-defining cancers are much more common among PLWH, such as anal carcinoma, Hodgkin lymphoma, hepatocellular carcinoma and lung cancer. The incidence of cancer among PLWH depending on various factors, virological control under combined antiretrovial therapies (cART), exposure prevention to oncogenic virus and toxics are of utmost importance, such as the implementation of specific screening programmes. Drug interactions between cART and oncologic treatments can lead to serious adverse effects or to a reduction in the therapeutic effects, therefore they require a close monitoring. The PLWH have been excluded from the oncologic clinical trials assessing the efficacy and toxicity profile of the immune checkpoints inhibitors (ICPi) because of an increased theoretical risk of inducing adverse events and a feared lack of efficacy in the immunocompromised population. However, the mostly retrospective clinical data reporting the use of ICPi among PLWH are somewhat reassuring with a safety and efficacy profile similar to what observed in HIV-negative patients. Regarding the "shock and kill" anti-HIV effects of ICPi, the preliminary clinical data available are still modest and relatively disappointing despite encouraging results obtained in vitro. HIV-associated cancers represent a particular care challenge due to the multiple comorbidities in the population and the high risk of drug interactions, thus the CANCERVIH national network is of particular interest within this context.L'infection par le VIH reste un problème majeur de santé publique en France et dans le monde. La survenue de cancer est fréquente chez les personnes vivant avec le VIH (PVVIH) et représente la première cause de mortalité dans cette population en France. Certains cancers non classant SIDA sont beaucoup plus fréquents chez les PVVIH, comme le carcinome anal, la maladie de Hodgkin, le carcinome hépatocellulaire et le cancer bronchique. Le risque de cancer chez les PVVIH dépendant de nombreux facteurs, le contrôle virologique, la prévention de l'exposition aux virus oncogènes et aux toxiques sont très importants, tout comme la mise en place de programmes de dépistage spécifiques. Les interactions médicamenteuses entre antirétroviraux et traitements antinéoplasiques pouvant entraîner un sur risque de toxicité ou une perte d'efficacité sont particulièrement à surveiller chez les PVVIH. Du fait d'un risque théorique accru de toxicité et de manque d'efficacité, les PVVIH ont été exclues des grandes études sur les inhibiteurs des checkpoints immunitaires (ICPi). Cependant, les données majoritairement rétrospectives sur l'utilisation des ICPi chez les PVVIH sont rassurantes avec un profil de toxicité et d'efficacité antitumorale similaire à celui observé en population générale. Quant à l'effet des ICPi dans une stratégie du « shock and kill » anti-VIH les tout premiers résultats disponibles dans la littérature semblent décevants malgré des résultats obtenus in vitro très encourageants. La complexité de prise en charge oncologique de cette population aux nombreux comorbidités nécessite une collaboration pluridisciplinaire étroite, le réseau national CANCERVIH prend tout son sens dans ce contexte

Reversible Tumor Progression Induced by a Dexamethasone Course for Severe COVID-19 during Immune Checkpoint Inhibitor Treatment

International audienceImmunotherapies and immune checkpoint inhibitors (ICI) represent the latest revolution in oncology. Several studies have reported an association between the use of corticosteroids and poorer outcomes for patients treated with ICIs. However, it has been never established whether corticoid-induced tumor progression under ICI treatment could be reversible. We report herein transient tumor progression induced by dexamethasone for a patient treated with pembrolizumab for metastatic bladder cancer. An 82-year-old man was treated with pembrolizumab as a second-line treatment for metastatic urothelial carcinoma with stable disease for 8 months as the best tumoral response. He experienced severe coronavirus disease 2019 (COVID-19) infection and was treated with high-dose dexamethasone for ten days according to the RECOVERY protocol. Following this episode, radiological CT-scan evaluation showed tumor progression. Pembrolizumab was maintained, and subsequent radiological evaluation showed tumor shrinkage. This case highlights that the antagonistic effect of glucocorticoids with ICI efficacy is transient and can be reverted when corticoids are withdrawn. Clinicians should be aware that tumor progression in the context of the intercurrent use of systemic corticosteroids can be temporary and should be interpreted with caution, and ICI continuation could be considered for some patients. Insights: The antagonistic effect of glucocorticoids with ICI efficacy is transient and can be reverted when corticoids are withdrawn. Tumor progression in the context of the intercurrent use of systemic corticosteroids can be temporary and should be interpreted with caution, and ICI continuation could be considered for some patients

Shared Decision-Making: a Systematic Review Focusing on Mood Disorders

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Brief report of Anti-PD1 in HIV setting: relevant and breaking results in first-line Non Small Cell Lung Cancer therapy

International audienceIn the recent past, we observed an increased risk of cancer in the HIV population due to the development of antiretroviral therapies that decreased mortality caused by HIV-specific infections. This particularly fragile population is frequently excluded from clinical trials, and up-to-date recommendations for these patients are lacking. Only few cases of HIV patients suffering from cancer and undergoing first-line immunotherapy have been reported so far. Here we report the largest known study of HIV patients with non-small cell lung cancer (NSCLC) (5 patients) undergoing first-line immunotherapy by pembrolizumab, following CANCERVIH group selection. Our results are consistent with previous case reports concerning safety of immunotherapy in HIV patients, showing no severe or fatal toxicity, opportunistic infections, or immune reconstitution inflammatory syndrome (IRIS). Moreover, pembrolizumab did not seem to modify HIV viral parameters. We also assessed effectiveness of immunotherapy in these HIV-immunosuppressed patients: the average survival was 9.8 months, with three patients showing rapid progression and two partial response. However, as well as safety and drug-to-drug interactions, the effectiveness of first-line immunotherapy in people living with HIV (PLWHIV) needs to be supported by larger studies

Association of TP53 mutations with response and longer survival under immune checkpoint inhibitors in advanced non-small-cell lung cancer

International audienceIntroduction: Tumor mutational burden (TMB) correlates with response to immune checkpoint inhibitors (ICI) in advanced non-small-cell lung cancer (aNSCLC). We hypothesized that TP53 mutations could reflect TMB and be associated with ICI benefit.Methods: TP53 mutations were assessed by next-generation sequencing in aNSCLC patients treated with programmed death-1 (PD-1) blockers. Clinical data, tumor programmed death ligand-1 (PD-L1) expression, and KRAS mutational status were collected. The primary endpoint was overall survival (OS).Results: In total, 72 patients (median [interquartile range] age: 61 [33-83] years) were included; 52 (72%) were male; 39 (54%) had performance status 0-1; 53 (74%) had adenocarcinoma; 20 (28%) received first-line ICI, 52 (72%) second line or more. In 65 patients with available data, 36 (55%) expressed PD-L1 in ≥50% of tumor cells, 20 (31%) in 1-49% of cells, and nine (14%) were PD-L1-negative. Non-synonymous TP53 mutations were observed in 41 (57%) and 25 (35%) harbored KRAS-mutated tumors. After a median follow-up of 15.2 months (95% confidence interval [CI] 10.3-17.4 m), the median OS in the TP53-mutated group was 18.1 months (95% CI 6.6-not reached), vs. 8.1 months (95% CI 2.2-14.5, hazard ratio [HR] = 0.48; 95% CI 0.25-0.95, p = 0.04) in the TP53-wild-type group. Median progression-free survival was significantly longer in TP53-mutated patients (4.5 months, 95% CI 2.8-18.1 versus 1.4, 95% CI 1.1-3.5; p = 0.03), although TP53 mutation status failed to significantly influence PFS in the multivariate analysis (p = 0.32). Objective response rate (ORR) was higher in patients with TP53 mutation (51.2% vs. 20.7%; p = 0.01). In multivariate analysis, TP53 mutations independently associated with longer OS (HR = 0.35, 95% CI 0.16-0.77, p = 0.009).Conclusions: TP53-mutated status correlated with immunotherapy OS benefit in aNSCLC

Reversal of immune-checkpoint inhibitor fulminant myocarditis using personalized-dose-adjusted abatacept and ruxolitinib: proof of concept

International audienceImmune-checkpoint inhibitors (ICI) have revolutionized cancer therapy but are associated with infrequent but lethal myocarditis, for which management remains uncertain. Abatacept, a CTLA-4 fusion protein targeting CD86 on antigen presenting cells and leading to global T-cell anergy, has been described as a potential treatment in individual reports. Yet, abatacept treatment dosage, schedule and optimal combination with other immunosuppressive therapies are unclear. We describe a 25-year-old man who developed pembrolizumab (anti-PD1)-induced myocarditis 14 days after first injection for thymoma treatment, which deteriorated into cardiogenic shock, with sustained ventricular arrhythmia, requiring urgent extracorporeal life support implantation, despite prompt initiation of corticosteroids and mycophenolate-mofetil. Using a strategy of serial measurement ensuring with a target of >80% CD86 receptor occupancy on circulating monocytes, abatacept dose was adjusted and combined with ruxolitinib and methylprednisolone. This strategy resulted in high-dose of abatacept: 60 mg/kg in three doses (20 mg/kg each) within the first 10 days, followed by two doses. Clinical improvement occurred within 7 days, with resolution of systolic cardiac dysfunction, and ventricular arrhythmias resulting in successful discharge from hospital. We reversed a case of nearly lethal ICI-myocarditis, using specific patient-dose adjusted abatacept, which may serve as basis for personalized treatment of patients with severe ICI-adverse events. Trial registration number: NCT04294771

18-FDG PET-CT diagnostic value in immune checkpoint inhibitor-induced myositis

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Vinorelbine thiotepa in metastatic breast cancer: a large real-life retrospective study

Vinorelbine thiotepa in metastatic breast cancer: a large real-life retrospective stud