Before the advent of neoadjuvant immunotherapy (IO) in macroscopic disease, IO and targeted therapies were recommended as adjuvant therapies for the treatment of stage III resectable melanoma. However, real-world evidence on their use and outcomes remains limited. This study described treatment patterns and survival outcomes among patients with stage III resectable melanoma who received adjuvant therapy in France. This retrospective cohort study used data from the exhaustive French national health data system (SNDS) to identify adults initiating adjuvant nivolumab (NIVO), pembrolizumab (PEM), or dabrafenib-trametinib (DT) between January 1, 2019, and December 31, 2021. Patients were followed until December 31, 2023, or death. Exclusion criteria included prior metastatic disease, other active cancers, or prior use of study drugs. Outcomes included treatment patterns at recurrence, described using Sankey diagrams, and survival (recurrence-free survival [RFS], overall survival [OS]), assessed using a Kaplan-Meier estimator. The study population consisted of 2612 patients with resected stage III melanoma initiating an adjuvant therapy. Of them, 1483 (56.8

8600 Background: Long-term (5-year) real-world overall survival (OS) in non–small cell lung cancer (NSCLC) remains poorly documented especially in prospective condition. The French nationwide KBP program comprises prospective cohorts conducted every 10 years since 2000 to evaluate lung cancer prognosis. In 2020, 8,941 patients were included across 81 non-academic public hospitals, with lung adenocarcinoma (LA) representing the most frequent histologic subtype. Building on previously reported 3-year survival results[1], we assessed temporal changes in 5-year OS and described the characteristics of long-term survivors with LC using the 2000, 2010, and 2020 cohorts. Methods: Patients with lung cancer, all stages, diagnosed in non-academic public hospitals in 2000, 2010, and 2020 were included in the French nationwide KBP cohorts, all conducted using the same prospective methodology. For the 2020 cohort, patient inclusion occurred between 1 January and 31 December 2020. Vital status was collected during follow-up. Five-year OS was estimated using the Kaplan–Meier method and compared across the 2000, 2010, and 2020 cohorts, overall and stratified by stage at diagnosis. In the 2020 cohort, a descriptive comparative analysis was performed between long-term survivors (≥5 years) and patients who died before this term. In the 2020 cohort, multivariable Cox proportional hazards models are ongoing to identify prognostic factors associated with OS. Prespecified covariates include age, sex, ECOG PS, smoking status, stage at diagnosis. These analyses remain preliminary and will be updated for the conference, as the 5-year vital status follow-up has recently been completed. Results: Among the 1,640, 3,199, and 5,009 patients with LA included in the 2000, 2010, and 2020 KBP cohorts, respectively, 5-year vital status was available for 99.3%, 96.2%, and 83.4% of patients. 5-year OS was 29.4% (95% CI, 28.1–30.7) in 2020, compared with 14.4% (95% CI, 13.3–15.7) in 2010 and 4.7% (95% CI, 3.0–7.2) in 2000, corresponding to an absolute improvement of 15.0% over the last decade. In the 2020 cohort, long-term survivors (≥5 years; n = 772) were 47.8% female, only six patients had an ECOG performance status ≥3, 48.2% were current smokers, 19.8% never-smokers and 32.0% former smokers. The distribution of stage at diagnosis among long-term survivors was 37.6% stage I, 9.9% stage II, 20.9% stage III, and 31.6% stage IV. Conclusions: 5-year real-world OS in LA has markedly improved over the last two decades with an increasing proportion of long-term survivors. Ongoing stage-stratified and multivariable analyses will further characterize long-term survival patterns. [1] https://evidence.nejm.org/doi/full/10.1056/EVIDoa2400443.

Almost all publications in biomedical literature have employed statistical tests, with p-values being considered of particular importance in the assessment of the presence of a link between two variables. However, these tests and p-values have been the subject of considerable criticism. It may appear paradoxical that tools utilised by the scientific community for nearly a century could possess all the flaws attributed to them. This paradox can partially be explained by the counterintuitive nature of p-values and the fact that the test that generates them is the result of a combination of two tests that were developed to answer statistical questions of a very different nature. The respective characteristics of these two tests are essentially unknown to the majority of users of p-values. The aforementioned paradox can be partially explained by the paucity of publications that seek to elucidate these concepts for users of p-values, the majority of whom are not statisticians. The recently introduced Bayesian methods have properties that enable us to understand the limitations of traditional methods. In Bayesian methods, the use of a specific interpretation of probability allows for better exploitation of clinical research data. The aim of this article is to highlight the limits of non-Bayesian methods and explain the principles and functioning of Bayesian methods to a non-statistical audience.

BACKGROUND:Cemiplimab an anti-programmed cell death receptor-1 antibody, was approved by the FDA and EMA for patients with locally advanced cutaneous squamous cell carcinoma (laCSCC) ineligible for curative surgery/radiotherapy or with metastatic (m) CSCC. TOSCA study evaluated the real-world effectiveness and safety of cemiplimab compared to historical systemic therapies (HSTs). METHODS:TOSCA (NCT05302297) was a large French retrospective, multicenter study comparing patient with la/mCSCC treated with cemiplimab via the early access program (EAP, 2018-2019) or HST (2013-2018). The primary endpoint was overall survival (OS); secondary endpoints were progression-free survival (PFS), duration of response (DoR), overall response rate (ORR), and safety. Effectiveness analysis using inverse probability weighting included a trial-like cohort of only immunocompetent patients meeting the EAP criteria to emulate a randomized clinical trial; safety analysis included all real-life patients. FINDINGS:The study included 280 real-life patients (cemiplimab: n = 147; HST: n = 133). The primary effectiveness analysis included a trial-like cohort (cemiplimab: n = 129; HST: n = 70; median age: 81 and 78 years, respectively). Median follow-up was 20 and 10 months in the cemiplimab and HST arms, respectively; median OS was 21.2 and 9.8 months, respectively (HR 95% CI: 0.57 [0.45-0.73]; P < 0.0001); median PFS was 13.7 and 5.3 months, respectively (HR [95% CI]: 0.57 [0.43-0.76]; P = 0.0001). Adverse drug reactions occurred in 27% of cemiplimab patients and 33% of HST patients. INTERPRETATION:TOSCA demonstrated better survival and response outcomes for cemiplimab versus HST in la/mCSCC; emphasizing, the importance of this retrospective studie in the absence of standard comparative trials.

Intravenous administration of anti-CTLA4 with anti-PD1 provides durable tumour responses but causes severe treatment-related adverse events in patients with cancer1. Intratumoural administration at lower doses but high local concentrations could enhance antitumour efficacy while minimizing systemic exposure and toxicity. Here we report the randomized multicentre phase 1b NIVIPIT trial (ClinicalTrials.gov: NCT02857569 ), which enrolled 61 patients with untreated metastatic melanoma, randomly assigned 2:1 to receive intravenous nivolumab (anti-PD1; 1 mg kg-1) combined with either intratumoural ipilimumab (anti-CTLA4; 0.3 mg kg-1) or intravenous ipilimumab (3 mg kg-1). The primary end-point was met with significantly lower incidence of grade 3 or 4 treatment-related adverse events at 6 months in the intratumoural versus intravenous arm (22.6% versus 57.1%), equivalent to anti-PD1 monotherapy. RECIST (response evaluation criteria in solid tumours) best objective response rate reached 65.7% for anti-CTLA4 injected lesions and 50% for uninjected lesions, confirming the relationship between intratumoural exposure to anti-CTLA4 and efficacy. Baseline tumour immune profiling revealed that protumoural activated regulatory T (Treg) cells and M2 macrophages predict durable clinical benefit, regardless of the anti-CTLA4 administration route. A decrease in activated intratumoural Treg cells occurred only in patients who showed durable clinical benefit, who also presented high intratumoural Fcγ receptor (FcγR) expression. Our results provide a rationale for intratumoural anti-CTLA4 strategies in oligometastatic and early-stage cancers and indicate that high intratumoural activated Treg cell and FcγR+ M2 macrophage numbers are prerequisites for efficacy of combined anti-CTLA4 and anti-PD1.

AIMS:Sodium-glucose co-transporter 2 inhibitors (SGLT2i) show a cardioprotective effect in heart failure and myocardial infarction, pathologies often associated with low-grade inflammation. This cross-sectional study aims to investigate whether low-grade inflammation regulates SGLT2 expression and function in human vasculature, heart, and endothelial cells (ECs). METHODS AND RESULTS:Human internal thoracic artery (ITA), left ventricle (LV) specimens, and cultured porcine coronary artery ECs were used. Expression of target molecules was assessed using RT-qPCR, western blot analysis, and immunofluorescence staining, and the generation of reactive oxygen species (ROS) and nitric oxide (NO) using fluorescent probes. The function of SGLT2 was investigated using empagliflozin and SGLT1 or 2 siRNA. SGLT2 mRNA and protein levels in ITA and LV specimens were correlated with the level of low-grade inflammation, markers of the angiotensin system, and EC activation. SGLT2 staining was observed in the ITA endothelium and smooth muscle, the coronary microcirculation, and cardiomyocytes. Elevated ROS formation in high SGLT2-expressing specimens was reduced by inhibition of the angiotensin system, SGLT2, and TNF-α. Exposure of ECs to IL-1ß, IL-6, and TNF-α led to an increase in SGLT1 and SGLT2 mRNA and protein expression, up-regulation of components of the angiotensin system, enhanced ROS and decreased NO formation, and activation of NF-κB. The stimulatory effect of TNF-α was prevented by N-acetylcysteine and inhibition of the angiotensin system, SGLT2 but not SGLT1, and NF-κB. CONCLUSION:Low-grade inflammation is closely associated with SGLT2 expression in human vasculature and heart, and this response contributes to a feedforward mechanism with the AT1R/NADPH oxidase pathway to cause eNOS-NO/ROS imbalance.

The aim of this study was to determine the prevalence of advanced hepatic fibrosis and to individualize using Bayesian analysis its associated risk factors in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) being cared for in three Alsatian cardio-metabolic health networks in the North East of France. Overall, 712 patients aged ≥18 years with a female predominance were included into a prospective, cross-sectional, and observational study. Advanced fibrosis and severe steatosis were evaluated using transient elastography (FibroScan®). The proportion of MASLD patients was 80% and 84% in women and men (difference -4.2% [-10.0; 1.9]), respectively. Advanced fibrosis was observed in 11% of patients, being more common in men (16.9%) than women (7.5%) (difference 9.4 [4.3-15.0]). Severe steatosis was also more common in men (74.9%) than women (63.4%) (difference 11.4 [4.2-18.2]). Only three of the tested variables were likely associated with advanced fibrosis: gender (OR: 1.78 [1.17-2.68]; Pr [OR >1] = 1), T2DM (OR: 1.54 [1-2.37]; Pr [OR >1] = 0.97) and hypertriglyceridemia (OR: 1.49 [0.97-2.27]; Pr (OR >1) = 0.97). In conclusion, this study confirmed the usefulness of assessing hepatic fibrosis in patients with metabolic dysfunction. Therefore, access to FibroScan® should be facilitated in all cardio-metabolic health networks.

Neoadjuvant immunotherapies have shown antitumor activity in melanoma. Substudy 02C of the global, rolling-arm, phase 1/2, adaptive-design KEYMAKER-U02 trial is evaluating neoadjuvant pembrolizumab (anti-PD-1) alone or in combination, followed by adjuvant pembrolizumab, for stage IIIB-D melanoma. Here we report results from the first three arms: pembrolizumab plus vibostolimab (anti-TIGIT), pembrolizumab plus gebasaxturev (coxsackievirus A21) and pembrolizumab monotherapy. Pathologic complete responses occurred in 10 of 26 patients (38%) with pembrolizumab plus vibostolimab, 7 of 25 (28%) with pembrolizumab plus gebasaxturev and 6 of 15 (40%) with pembrolizumab monotherapy. Major pathologic responses occurred in 13 (50%), 10 (40%) and 7 (47%) patients, respectively. Safety was manageable. Treatment-related adverse events occurred in 24 of 26 patients (92%) with pembrolizumab plus vibostolimab, 21 of 25 (84%) with pembrolizumab plus gebasaxturev and 12 of 15 (80%) with pembrolizumab monotherapy; grade 3 or 4 treatment-related adverse events occurred in 2 (8%), 7 (28%) and 1 (7%) patient in each arm, respectively. No deaths due to adverse events occurred. Exploratory objective responses per RECIST v1.1 were observed in 13 (50%), 8 (32%) and 4 (27%) patients, in each arm, respectively. In a post hoc analysis, scores for tumor mutational burden and an 18-gene T cell-inflamed gene expression profile were generally higher in patients with major pathologic response. Longer follow-up will provide insight into the incremental benefit of combining neoadjuvant pembrolizumab with other therapies in stage IIIB-D melanoma. ClinicalTrials.gov registration: NCT04303169 .

The MTOR inhibitors have demonstrated antiviral properties, and prior non-randomized studies have suggested they may have a suppressive effect on BKPyV replication. Here, in this randomized, multicenter, controlled trial (BKEVER study), we sought to evaluate the impact of everolimus (EVR) in facilitating the clearance of BKPyV compared to simply reducing immunosuppression among kidney transplant recipients (KTRs). All together, 130 KTRs presenting with BKPyV DNAemia were randomized 1:1 into two groups. The EVR group, in which mycophenolate mofetil (MMF) was replaced by EVR along with a decrease in calcineurin inhibitor trough levels and secondly the MMF group, in which the MMF dose was decreased by half along with a similar lowering of calcineurin inhibitor levels. The primary endpoint was the proportion of patients achieving viral clearance at six months. Secondary endpoints included the kinetics of BKPyV replication over time, the incidence of BKPyV-associated nephropathy, kidney graft function, the incidence of kidney graft rejection, and medication tolerability over two years. Significantly, BKPyV clearance was achieved in 55.7% of patients in the EVR group compared to 81.3% of patients in the MMF group at six months. The reduction in BKPyV DNA load was significantly more rapid in the MMF group. Calcineurin inhibitor trough levels were within expected target ranges and did not differ meaningfully between the two groups from randomization through month six. Two grafts were lost, and four patients died. Eleven patients in the EVR group and six patients in the MMF group developed biopsy-proven BKPyV nephropathy. Thus, in KTRs with BKPyV DNAemia, replacing MMF with EVR along with lowering calcineurin inhibitor levels did not lead to more frequent or faster clearance of BKPyV.

Resistance to immune checkpoint inhibitors (ICI) in cancer patients is not fully understood, and predictive biomarkers are lacking. MELANFα (NCT03348891) is an open‐label, prospective, multicenter cohort of 60 patients with advanced melanoma receiving ICI (bitherapy: ipilimumab + nivolumab; monotherapy: pembrolizumab or nivolumab). The primary objective was to evaluate whether changes in plasma TNF between baseline (W0) and week 12 (W12) identified patients with non‐progressive disease at W12. Secondary and exploratory objectives were to assess the association between plasma TNF, tumor response, and changes in circulating T cells. Plasma TNF increased along therapy, but its W12/W0 fold change was not associated with non‐progressive disease at W12. However, plasma TNF levels at W12 were significantly higher in non‐responders than in responders across therapies ( p = .0129). The remodeling of circulating T cell subpopulations was mostly triggered by bitherapy. Increased proportions of circulating central memory and effector memory CD8 T cells after bitherapy were positively and negatively associated with response to treatment, respectively. In this cohort, circulating T cells from responders and non‐responders also displayed distinct molecular characteristics. Indeed, responders showed an increased proportion of CD8 T cells with low enrichment of TNF‐related pathways and high cytotoxic potential, while non‐responders displayed increased proportions of circulating CD8 EM T cells enriched for TNF‐related pathways and directed toward cytokine expression. In conclusion, our study shows that elevated plasma TNF and enriched TNF pathways in T cells are associated with poorer clinical outcomes, reinforcing the notion that TNF may dampen ICI efficacy.

Background: COVID-19 is associated with an increased risk of cardiovascular complications. Although cytokines have a predominant role in endothelium damage, the precise molecular mechanisms are far from being elucidated. Objectives: The present study hypothesized that inflammation in patients with COVID19 contributes to endothelial dysfunction through redox-sensitive SGLT2 overexpression and investigated the protective effect of SGLT2 inhibition by empagliflozin. Methods: Human plasma samples were collected from patients with acute, subacute, and long COVID-19 (n = 100), patients with non-COVID-19 and cardiovascular risk factors (n = 50), and healthy volunteers (n = 25). Porcine coronary artery endothelial cells (ECs) were incubated with plasma (10%). Protein expression levels were determined using Western blot analyses and immunofluorescence staining, mRNA expression by quantitative reverse transcription-polymerase chain reaction, and the level of oxidative stress by dihydroethidium staining. Platelet adhesion, aggregation, and thrombin generation were determined. Results: Increased plasma levels of interleukin (IL) -1(3, IL -6, tumor necrosis factor-alpha, monocyte chemoattractant protein -1, and soluble intercellular adhesion molecule -1 were observed in patients with COVID-19. Exposure of ECs to COVID-19 plasma with high cytokines levels induced redox-sensitive upregulation of SGLT2 expression via proinflammatory cytokines IL -1(3, IL -6, and tumor necrosis factor-alpha which, in turn, fueled endothelial dysfunction, senescence, NF-kappa B activation, inflammation, platelet adhesion and aggregation, von Willebrand factor secretion, and thrombin generation. The stimulatory effect of COVID-19 plasma was blunted by neutralizing antibodies against proinflammatory cytokines and empagliflozin. Conclusion: In patients with COVID-19, proinflammatory cytokines induced a redoxsensitive upregulation of SGLT2 expression in ECs, which in turn promoted endothelial injury, senescence, platelet adhesion, aggregation, and thrombin generation. SGLT2 inhibition with empagliflozin appeared as an attractive strategy to restore vascular homeostasis in COVID-19.

Background: The epidemiological and immunopathogenic association between Sjögren disease (SD) and non-Hodgkin’s lymphoma (NHL) is well-established. However, the epidemiological data on this complication mostly relies on data from tertiary centers, introducing selection bias and limiting comprehensive case capture. Objectives: This study aimed to evaluate accurately the characteristics of lymphoma in primary or associated SD using data from the French nationwide healthcare information system (“système national des données de santé” [SNDS]). Methods: SD patients were identified in the SNDS database based on a validated algorithm [1] (ICD10 code for SD and reimbursement for at least 2 SD-prescribed drugs). Primary SD was defined in the absence of an ICD10 code for other autoimmune diseases, and associated SD was defined otherwise. The study analyzed, primary, associated and all SD patients and lymphoma occurrences between 2009 and 2022. Analysis of risk factors of lymphoma included demographic variables such as age, sex, disease duration, and proxy reflecting disease activity including notably cryoglobulinemic vasculitis and monoclonal gammopathy of unknown significance (MGUS). Results: •Patients with primary SD•In the 30,221 patients with primary SD (65.7% of the total cohort of patients with SD; 88.8% women, median age 60 [48;70], median follow-up 11.6 years [9.4;13.2]; hydroxychloroquine use in 35.1%, methotrexate [11.5%], leflunomide [1.2%], azathioprine [4.4%], mycophenolate [3.1%], cyclophosphamide [0.4%], and rituximab [5.5%]), lymphoma occurred in 1228 patients with a prevalence of 4.1%. Marginal zone lymphomas (MZL) were the predominant lymphoma subtype (53.8%) (especially MALT-MZL [30.9%]) followed by diffuse large B-cell lymphoma (DLBCL) (25.4%), follicular lymphoma (FL) (12.1%), Hodgkin’s lymphoma (8.2%), and T/NK lymphoma (7.2%). Mortality was higher in patients with lymphoma (379/1228 [30.9%] versus 4335/28993 [15%], p<0.001). Preliminary risk factor analysis revealed associations with MGUS and cryoglobulinemic vasculitis: MGUS was observed in 3.2% of SD patients without lymphoma, compared to 10.8% in those with lymphoma (p < 0.001), and cryoglobulinemic vasculitis occurred in 2.2% of SD patients without lymphoma, as compared with 10% of patients with lymphoma (p < 0.001).•Patients with associated SD•In the 15,791 patients with associated SD (34.3% of the total cohort, including rheumatoid arthritis [20.4%], systemic lupus [10%], systemic sclerosis [6.2%], other connective tissue disorders [3.2%], and juvenile arthritis [0.3%]), 483 patients developed lymphoma (3.1%).•Total SD cohort•In the total SD cohort, including 46,012 patients with either primary or associated SD (89.4% women, median age 59 [47;69], median follow-up 11.8 years [9.5;13.2]), lymphoma occurred in 1749 patients, with a 3.8% prevalence. Lymphoma subtypes were distributed similarly to the primary SD cohort, and associations between lymphoma and MGUS and cryoglobulinemic vasculitis were observed. Mortality was higher in patients with lymphoma compared to those without lymphoma (30.9% versus 14.8% [p < 0.001]). Conclusion: This extensive epidemiological nationwide study demonstrates a 4% prevalence of lymphoma in primary SD, and 3% prevalence in associated SD. Preliminary risk factor analysis confirms the association between SD-related lymphoma and MGUS and cryoglobulinemic vasculitis. REFERENCES: [1] Seror et al. (2024 in press) Development of an Algorithm to Identify Sjögren’s Syndrome Patients in the French National Healthcare Claims Database. RMD Open. Acknowledgements: NIL. Disclosure of Interests: None declared.

BACKGROUND AND AIMS:Parental guidance is essential for supporting parental involvement, maintaining the quality and safety of infant care, and limiting parental stress. The efficiency of a new tool to support parental empowerment - "Step by step with my baby" - was evaluated. The perception of this tool by parents and nurses was studied. METHODS:This was a prospective, observational study conducted from September 2019 to December 2020 at a level-3 neonatal center. A total of 79 newborns (<33 weeks of gestational age or small for gestational age), 84 parents, and 94 nurses were included. The new tool that was evaluated is in the form of a drawing of flowers to be colored according to the parents' ability to care for their newborn. Six domains were explored and given a score (total of 35 points) according to the parents' ability to care for each item: behavior, skin-to-skin contact, carrying, oral and tube feeding, and routine care. The use and relevance of this tool were evaluated by parents and caregivers. RESULTS:At a mean of 19 days of life, parents required caregiver support regardless of the skill domain (6/35). After 26 days, the mean score increased to 19.4 (p < 0.05). Parents felt autonomous in changing diapers and monitoring temperature but always required help for skin-to-skin contact, carrying, and feeding with or without a tube. The progression was not affected by the presence of siblings, the distance from home, and staying in the parental hospital room. For 67 % of the parents, the tool gave them a better understanding of their newborn and helped them be more confident (69 %) without feeling judged (81 %). These feelings were upheld by nurses. CONCLUSIONS:This tool was efficient for evaluating parents' autonomy and helped them take ownership of the care provided.

Abstract Background: Pembrolizumab (pembro) monotherapy demonstrated clinically meaningful antitumor activity for both locally advanced (LA) and recurrent or metastatic (R/M) cutaneous squamous cell carcinoma (cSCC) in the phase 2 KEYNOTE-629 trial (NCT03284424). cSCC has high immunogenicity driven by a high tumor mutational burden and it is of interest to determine if the 18-gene T-cell inflamed gene expression profile (TcellinfGEP) and a set of other signatures relevant to the tumor microenvironment are associated with response to treatment. This retrospective analysis aimed to evaluate the association between GEP signatures and clinical outcomes in patients (pts) treated with pembro in KEYNOTE-629. Methods: Pts with histologically confirmed LA or R/M cSCC, measurable disease per RECIST v1.1, ECOG PS 0 or 1 received pembro 200 mg IV Q3W ≤35 cycles. Association between TcellinfGEP by RNAseq with clinical response (objective response rate [ORR], progression-free survival [PFS], and overall survival [OS]) to pembro, and association between a set of additional consensus signatures with clinical response to pembro adjusted for TcellinfGEP were evaluated. Significance of GEP signatures was prespecified at 0.05 for 1-sided P values from logistic (ORR) and Cox proportional hazard regression (PFS, OS) adjusted for ECOG PS. Additional assessments included TcellinfGEP AUC or Harrell’s C-index in predicting response to pembro. Results: Of 159 pts, 143 (n = 52, LA cSCC; n = 91, R/M cSCC) had RNAseq samples available for analysis. Of 143 pts, 33.6 % had a TcellinfGEP <1st tertile and 66.4% had a TcellinfGEP ≥1st tertile. TcellinfGEP was significantly associated with improved ORR (P = 0.040) but not PFS (P = 0.087) or OS (P = 0.709). None of the 10 other consensus signatures were significantly associated with clinical outcomes after adjusting for TcellinfGEP and multiplicity (P > 0.05). AUC of TcellinfGEP was moderately predictive of ORR (0.61, 95% CI, 0.51-0.70). Harrell’s C-index of TcellinfGEP was moderately predictive of PFS (0.57, 95% CI 0.51-0.63), and duration of response (0.56, 95% CI 0.38-0.73), but not predictive of OS (0.50, 95% CI 0.42-0.57). Median PFS (95% CI) was 4.1 mo (1.4-9.8) for the TcellinfGEP <1st tertile subgroup and 8.5 mo (5.5-21.0) for TcellinfGEP ≥1st tertile subgroup. Median OS (95% CI) for the TcellinfGEP <1st tertile subgroup was 25.1 mo (11.4-NR) and 21.0 mo (15.8-29.8) for the TcellinfGEP ≥1st tertile subgroup. Conclusions: In this retrospective analysis of KEYNOTE-629, Tcellinf GEP was associated with tumor objective response to pembro, but was not clearly associated with longer survival in pts with LA or R/M cSCC treated with pembro. While definitive conclusions require more analyses, these findings provide additional support for TcellinfGEP as a predictive biomarker for cSCC. Citation Format: Åse Bratland, Jean-Jacques Grob, Eva Munoz Couselo, Laurent Mortier, Ralf Gutzmer, Osama Roshdy, Rene Mendoza Gonzalez, Jacob Schachter, Ana M. Arance Fernandez, Florent Grange, Nicolas Meyer, Abhishek J. Joshi, Salem Billan, Judong Shen, Razvan Cristescu, Michael Nebozhyn, Andrey Loboda, Jason Sparkowski, Burak Gumuscu, Jianda Yuan, Brett Hughes. Association of gene expression profiles and clinical outcomes in patients with locally advanced or recurrent/metastatic cutaneous squamous cell carcinoma treated with pembrolizumab in KEYNOTE-629 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT207.