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Background Neoadjuvant cisplatin-based chemotherapy (NAC) is the standard of care in non-metastatic muscle-invasive bladder cancer (MIBC). However, 60-75% patients have residual tumor after neoadjuvant cisplatin-gemcitabin or ddMVAC regimen. Pathological complete response (pCR) after NAC is correlated with overall survival (OS). Based on the overall response rate observed in the metastatic setting, ddMVAC is the most commonly used NAC regimen in Europe in urothelial carcinoma (UC) in fit patients. The emergence of immune checkpoint inhibitor (ICI) in the metastatic setting raises the question if the combination chemo plus ICI could increase the pCR rate. Trial design NEMIO is a French open-label randomized phase II trial assessing in the neoadjuvant setting the combination ddMVAC plus durvalumab (D) alone or in combination with tremelimumab (T): 4 cycles of ddMVAC every 2 weeks + 2 cycles of D (1500 mg) +/- T (75 mg) every 4 weeks. Cystectomy is performed 4-8 weeks after the last dose of ddMVAC. As no safety data are available on the ICI plus ddMVAC combination, 6 pts will be included in each arm in a safety run-in cohort to evaluate the toxicity rate of the 2 regimens. Each arm will be expanded to a maximum of 60 pts according to a Bayesian stopping rule based on grade 3/4 treatment-related adverse events (G 3/4 TRAE). The primary endpoint of the safety run-in phase will be the rate of G3/4 TRAE. The primary endpoint of the phase II will be the pCR rate and G3/4 TRAE. We hypothesized that pCR after ddMVAC + D +/- T will be > or = 45%. Exploratory endpoints will include biomarkers of response and resistance to the combo. Molecular analysis will be conducted on tumor, blood (ctDNA) and urine samples (uDNA). Immunological and metabolomics profile will also be analyzed. Seven patients have yet been enrolled since December 2018 from the 10 French participating centers and we expect the recruitment to be completed in 2021. Clinical trial identification NCT03549715. Legal entity responsible for the study Association pour la Recherche de Therapeutiques Innovantes en Cancerologie (ARTIC). Funding AstraZeneca. Disclosure C. Thibault: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self), Advisory / Consultancy: BMS; Travel / Accommodation / Expenses: Roche; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Sanofi; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Janssen; Honoraria (self), Advisory / Consultancy: Astellas; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer. D. Borchiellini: Advisory / Consultancy, Research grant / Funding (institution): Roche; Advisory / Consultancy, Research grant / Funding (institution): MSD; Advisory / Consultancy: BMS; Advisory / Consultancy: Pfizer; Advisory / Consultancy, Research grant / Funding (institution): Janssen; Advisory / Consultancy, Research grant / Funding (institution): Astellas; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Ipsen. O. Huillard: Honoraria (self): AstraZeneca; Honoraria (self): BMS; Honoraria (self): Janssen. P. Barthelemy: Advisory / Consultancy: BMS; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Roche; Advisory / Consultancy: Janssen; Advisory / Consultancy: MSD; Advisory / Consultancy: Ipsen; Advisory / Consultancy: Novartis; Advisory / Consultancy: Sanofi. D. Pouessel: Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy, Research grant / Funding (institution): Janssen; Research grant / Funding (institution): MSD; Research grant / Funding (institution): Roche; Research grant / Funding (institution): Incyte. A. Flechon: Advisory / Consultancy: BMS; Advisory / Consultancy: Pfizer; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Roche; Advisory / Consultancy: MSD. H. Blons: Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Boehringer; Advisory / Consultancy: MSD. S. Oudard: Honoraria (self): BMS; Honoraria (self): MSD; Honoraria (self): AstraZeneca; Honoraria (self): Roche. All other authors have declared no conflicts of interest.

Background We investigated whether Imunoscore performed on localized or locally advanced urothelial carcinoma (UC) tumor samples could predict response to neoadjuvant chemotherapy and survival outcome. Methods This retrospective ongoing study evaluated the Immunoscore in 150 patients with UC (140 UC of the bladder, 10 UC of the upper tract) from 6 centers (Greece and France). All patients underwent neo-adjuvant chemotherapy. Pre-treatment tumor samples (trans-urethral resection or upper tract biopsy) were immunostained for CD3+ and CD8+ T cells and quantified by digital pathology to determine the Immunoscore. The consensus Immunoscore was applied to tumors with invasive margin and an Immunoscore adapted to samples quantified when no invasion was identified on the specimen. Results were correlated with response to neoadjuvant treatment and time to recurrence (TTR). Results Immunoscore Low, Intermediate and High were respectively observed in 40, 43 and 17% of the cohort. Densities of CD3 and CD8 in the center and invasive margin were not significantly different according to clinical parameters such as T-stage, N-stage, age, gender, tumor differentiation (with or without variant), and localization (upper tract versus bladder). Immunoscore was positively and significantly correlated with TTR. High, intermediate and low Immunoscore patients had a median TTR of 83, 34 and 27 months, respectively (P Conclusions The results of this ongoing study show a significant prognostic and potentially predictive role of Immunoscore in UC patients with important therapeutic implications. These preliminary results will be completed as samples are being analyzed before ESMO 2019 annual meeting. Legal entity responsible for the study The authors. Funding FONCER. Disclosure C. Thibault: Honoraria (self), Travel / Accommodation / Expenses: Astellas Pharma; Honoraria (self): Ipsen; Advisory / Consultancy, Travel / Accommodation / Expenses: Janssen-Cilag; Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy, Research grant / Funding (institution): Sanofi Pasteur; Research grant / Funding (institution), Travel / Accommodation / Expenses: AstraZeneca/Medimmune; Travel / Accommodation / Expenses: Astellas; Travel / Accommodation / Expenses: Roche/Genentech. F. Hermitte: Shareholder / Stockholder / Stock options, Full / Part-time employment: HalioDx. A. Bamias: Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): BMS; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Pfizer; Advisory / Consultancy, Research grant / Funding (self): AstraZeneca; Advisory / Consultancy, Research grant / Funding (self): Ipsen; Research grant / Funding (self): Lilly; Research grant / Funding (self): Astellas. J. Galon: Advisory / Consultancy, Research grant / Funding (institution), Shareholder / Stockholder / Stock options: HalioDx; Honoraria (self): AstraZeneca; Honoraria (self): Novartis; Honoraria (self): Merck; Honoraria (self): MSD; Honoraria (self): BMS; Honoraria (self): Sanofi; Honoraria (self): Gilead; Advisory / Consultancy, Research grant / Funding (institution): Io Biotech; Advisory / Consultancy: Illumina; Advisory / Consultancy: Northwest Biotherapeutics; Advisory / Consultancy: Actelion; Advisory / Consultancy: Amgen; Research grant / Funding (institution): Perkin Elmer; Research grant / Funding (institution): MedImmune; Research grant / Funding (institution): Janssen; Research grant / Funding (institution): Imcheck; Licensing / Royalties: INSERM. All other authors have declared no conflicts of interest.

Background To describe better the clinical, biological, endoscopic and pathological presentations, as well as the outcome, of primary follicular lymphoma (FL) of the gastrointestinal (GI) tract. Patients and methods From November 1983 to February 2001, 25 eligible patients with primary FL of the GI tract were retrieved from several French Departments of Pathology departments based on histological diagnosis and immunophenotype. Median age was 56 years (range 44–71) with a sex ratio female/male of 2 (17/8). Results Abdominal pain was the main presenting symptom followed by intestinal obstruction. The small intestine was the most common site of involvement. Lesions were unifocal in the majority of patients (15/25). A pattern similar to lymphomatous polyposis was observed in 50% (7/14) of patients. Twelve patients had stage I, 10 patients stage II and three patients stage IV disease, and there was minimal extra intestinal involvement. Lymphoma tissues were composed of neoplastic follicles, most of which were grade 1 according to the World Health Organization (WHO) classification. The immunophenotype of the lymphoma cells was CD20+, CD10+, bcl2+ and CD5–. In tissue samples, IgH/bcl2 rearrangement at the MBR locus was present in 11 of14 patients tested. Seven patients did not receive any treatment; four of them progressed after a medianfollow-up of 37.5 months. Treatment was otherwise heterogeneous, and complete remission was obtained in 15 patients which lasted for a median of 31 months. Relapses were either in the GI tract (n = 3) or outside the GI tract (n = 3). After a median follow-up of 34 months (range 5–203), 22 patients were still alive (complete remission, 11; partial remission, three; stable disease, six; progressive disease, two). Conclusions Primary FL of the GI tract is a predominantly female lymphoma that most frequently involves the small intestine. Since the endoscopic and clinical presentation may not be different from lymphomatous polyposis, which is often associated with mantle cell origin of tumor cells, it is mandatory to perform an immunohistological and, if possible, a molecular analysis of GI lymphoma. The course of the disease is indolent and does not differ from nodal FL. Thus, therapy may not be required unless significant clinical symptoms are present or until disease progression.

Aim: New clinical tools are needed to improve risk assessment in ccRCC. The 16-gene (11 cancer related, 5 reference) Recurrence Score (RS) was developed in a cohort of 931 stage I-III ccRCC patients (pts) from Cleveland Clinic. A large prospectively-designed clinical validation study of the RS in stage I-III ccRCC pts diagnosed from 1995 to 2007 at the French consortium was recently reported. The present analysis assesses the performance of the score in clinically relevant subgroups. Methods: The genes, algorithm, endpoints, methods, and analysis plan were pre-specified prior to merging clinical and molecular data. RT-PCR in fixed paraffin-embedded primary ccRCC tissue was performed without knowledge of clinical data. Recurrence-free interval was analyzed using Cox regression stratified by stage with data censored at 5 years, and Kaplan-Meier methods. Results: RS was successfully generated in 626/645 pts (97%): 398 stage I, 54 stage II, 174 stage III. Most (71%) patients were male, 29% were 70 years or older, 36% with partial nephrectomy, 46% with tumors ≤4 cm, 65% with Fuhrman grade 3-4, and 27% with invasion. Median follow-up was 5.5 yrs. The continuous RS predicted recurrence risk (HR per 25 point increase in RS (HR/25) =3.9, 95% CI 2.6-5.8, p 7cm), Fuhrman grade, and presence/absence of invasion (all interaction p > 0.29). Conclusions: The 16-gene RS is validated as a predictor of clinical outcome in pts with stage I-III ccRCC and provides significant information beyond conventional pathologic measures. The performance of the score was similar across a wide range of clinically relevant covariates indicating potential broad utility. Disclosure: B. Escudier: has an interest in relation with Genomich Health for sponsored research; M. Lopatin: is an employee of Genomic Health; C. Svedman: I am an employee of Genomic Health; T. Tsiati, M. Bonham, D. Knezevic and A. Goddard: Employee of Genomic Health; T. Lebret: Part of research grant from Genomic Health to perform the study (with the IGR institution, not personally); A. Mejean: Part of research grant from Genomic Health to perform the study (with the IGR institution, not personally). All other authors have declared no conflicts of interest.