Jacques Cadranel

Experimental data suggest that COVID-19 vaccination could modulate immune checkpoint inhibitor (ICI) effects, but population evidence is limited. Using the French health data system (Système National des Données de Santé), we identified 95,015 adults initiating ICI therapy between December 2020 and March 2023. We assessed mRNA vaccination within 100 days before ICI initiation using inverse probability of treatment weighting and within 100 days after ICI initiation among previously unvaccinated patients using a cloning–censoring–weighting target-trial emulation. The primary outcome was all-cause mortality; secondary outcomes were cancer-specific and non-COVID-19 mortality. Follow-up extended to 31 December 2024 for all-cause mortality and to 31 December 2023 for cause-specific deaths. Pre-ICI mRNA vaccination was associated with lower early all-cause mortality (hazard ratio (HR) 0.90 (95% confidence interval (CI) 0.87–0.94) at 1–3 months and 0.96 (0.93–1.00) at 6 months) and no significant association after 12 months. Post-ICI mRNA vaccination showed a similar early association (HR 0.84 (95% CI 0.80–0.88) at 3 months and 0.86 (0.79–0.94) at 6 months), also with no significant association after 12 months. Estimates for non-COVID-19 and cancer-specific mortality were similar to those for overall survival. Similar early patterns with non-mRNA COVID-19 and other adult vaccines suggest modest, transient associations or healthy-vaccinee effects, rather than a specific mRNA COVID-19 vaccine effect.

COPA syndrome is a rare monogenic autoinflammatory disease due to heterozygous mutations in COPA, encoding the coatomer subunit α. COPA syndrome demonstrates phenotypic overlap with STING-associated vasculopathy with onset in infancy (SAVI), the latter due to gain-of-function mutations in STING1. Indeed, STING activation is a key driver of the pathogenesis of COPA syndrome, and a recent report suggested that the presence of the common HAQ STING allele confers complete protection against the development of clinical disease in the context of pathogenic heterozygous mutations in COPA. Given the potential significance of this result for patient management, we investigated the STING HAQ haplotype status of a separate cohort of individuals segregating pathogenic mutations in COPA. In doing so, we ascertained five HAQ-negative, clinically asymptomatic individuals aged 30, 39, 39, 42, and 43 years at last evaluation, and an HAQ-positive male with kidney disease that we consider most likely attributable to the recurrent R233H mutation in COPA. Our findings challenge the suggestion that STING haplotype status is the sole determinant of clinical penetrance in COPA syndrome.

We assessed long‐term trends in cancer incidence among people with HIV (PWH) in France between 1997 and 2018, focusing on AIDS‐defining cancers (ADC) (Kaposi's sarcoma, non‐Hodgkin's lymphoma, and cervical cancer), three virus‐related non‐AIDS‐defining cancers (Hodgkin lymphoma, liver, and anal cancer), and four virus‐unrelated cancers (lung, colorectal, prostate, and breast cancer). Using data from the ANRS CO4‐French Hospital Database on HIV and cancer registries in the general population, we calculated age‐standardized incidence rates and standardized incidence ratios (SIRs) across four time periods. Special attention was given to PWH with controlled viral load and restored CD4 during 2008–2018. Among 154,733 individuals contributing nearly 2 million person‐years, 9572 cancers were diagnosed. Incidence rates of ADC and virus‐related non‐ADC declined over time but remained significantly higher than in the general population, with SIRs ranging from 3 to 420, even in recent years. Rates of prostate and colorectal cancers increased overtime, while breast cancer incidence remained stable. For these three cancers, the relative risk compared to the general population remained close to 1. In PWH with CD4 ≥ 500/mm ³ for at least 2 years and with recent viral load ≤50 copies/mL, risks of virus‐related cancers (KS, NHL, HL, liver, and anal cancer) remained significantly higher relative to the general population, albeit to a lesser extent than in PWH overall, while risks of lung and cervical cancers were similar. Over 20 years, the incidence of all virus‐related cancers continued to fall but in the most recent period, the risks still remained higher than in the general population.

Background: Recurrent respiratory papillomatosis (RRP) is a rare respiratory disease primarily caused by chronic human papillomavirus (HPV) infection of serotypes 6 and 11. It manifests in childhood (juvenile-onset recurrent respiratory papillomatosis (JoRRP)) and adulthood (adult-onset recurrent respiratory papillomatosis (AoRRP)), leading to progressive obstruction by papillomas in the upper airway and occasionally in the lower respiratory tract (LRT), including the lungs, with a potential for malignant transformation. This study aimed to delineate the characteristics of JoRRP and AoRRP with LRT involvement in adulthood.Methods: A multicentre French-speaking cohort study was conducted, coupled with a comprehensive literature review of clinical, histological, therapeutic and prognostic features associated with RRP with LRT involvement.Results: Among the 122 cases of RRP with LRT involvement analysed, 55 (45%) had JoRRP and 67 (55%) had AoRRP. The mean age at diagnosis was 4 years for JoRRP and 54 years for AoRRP. Ear, nose and throat involvement was observed in all JoRRP cases and in 34 AoRRP cases (51%). Lung involvement occurred in 47 JoRRP cases (85%) and in 10 AoRRP cases (15%). Malignant transformation to squamous cell carcinoma in the trachea (n=6) or lung (n=36) was observed in 42 patients (34%). Factors associated with lung involvement included JoRRP, repeated debulking and malignant transformation; the only factor associated with malignant transformation was lung involvement. Overall mortality was 16%, with JoRRP, lung involvement and malignant transformation identified as risk factors for death.Conclusion: This study highlights the prevalence of lung involvement and malignant transformation in RRP with LRT involvement and advocates for targeted screening measures and preventive therapeutic strategies.

Background: Real‐world data regarding patients with non‐small cell lung cancer (NSCLC) with EGFR exon 20 insertion (ex20ins) mutations receiving mobocertinib are limited. This study describes these patients' characteristics and outcomes.Methods: A chart review was conducted across three countries (Canada, France, and Hong Kong), abstracting data from eligible patients (NCT05207423). The inclusion criteria were: ≥ 18 years old; diagnosis of stage IIIB‐IV NSCLC with EGFR ex20ins between January 1, 2017 and November 30, 2021; received mobocertinib. Data on demographics, clinical parameters, treatment patterns, mobocertinib exposure, real‐world outcomes, and adverse events (AEs) were collected. Results are also reported by Asian/Non‐Asian races.Results: Overall, 105 patients were enrolled (median [IQR] age at initial diagnosis: 64.0 years [56, 71]; women: 62.9%). The most common first‐line of therapy (LoT) was chemotherapy; the most common second LoT was EGFR tyrosine kinase inhibitors. Most patients received mobocertinib during LoT two and three (74.3%); the maximum dose was 160 mg/day for 67.6% of the cohort (mean [SD] daily dose: 130.6 mg [36.68]). The median real‐world progression‐free survival (PFS) on mobocertinib was 4.76 months (95% CI: 3.98, 6.21). The overall response rate and disease control rate were 20.0% and 48.6%, respectively (median duration of response: 8.34 months [95% CI: 3.61, 9.49]). The median overall survival (OS) was 26.28 months (95% CI: 20.21, 36.44). Asian patients had numerically superior PFS and OS compared with non‐Asian patients. Regarding safety analysis, 73 patients (69.5%) experienced any AE. The most common AE was diarrhea (any grade) (52 patients; 49.5%).Conclusions: These data illustrate the real‐world effectiveness of mobocertinib.

Background: Pulmonary sarcomatoid carcinomas (PSC) are notorious for their poor prognosis and resistance to chemotherapy. The literature suggests that immunotherapy might be effective against this aggressive tumor. This study aims to evaluate the efficacy of immunotherapy, either alone or combined with chemotherapy, as first-line treatment for PSC patients. Methods: In a retrospective, multicentric, real-world study conducted between July 2017 and April 2021, patients with stage III (ineligible for surgery or radio-chemotherapy) or stage IV PSC were enrolled. These patients received their first-line treatment with immunotherapy and were categorized into two groups based on their treatment modality: the immuno-chemotherapy (IO CT) group or the immunotherapy-alone (IO) group. Results: This study analyzed a population of 34 patients from eight different hospital centers. In this cohort, the objective response rate (ORR) was 56%, median duration of response was 20.5 months, median progression-free survival (PFS) was 5.11 months, and median overall survival (OS) 13.9 months. Demographic characteristics remained consistent among the treatment groups except for the age (54.0- and 71.0-year-old in the IO CT and IO group, respectively, P=0.02). The IO CT group demonstrated an ORR of 64.0%, a median PFS at 8.72 months, and a median OS of 16.08 months, while the IO group displayed respective values of 52.0%, 3.45 months, and 13.11 months. Conclusions: This study showed the potential efficacy of immunotherapy as a first-line treatment for PSC. While acknowledging the retrospective nature of the study, our findings suggest a trend favoring the combination of IO CT over IO alone in these patients.