PEG-FILGRASTIM AFTER AUTOLOGOUS PERIPHERAL BLOOD STEM CELL TRANSPLANTATION : A SINGLE-CENTRE EXPERIENCE

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PEGYLATED-FILGRASTIM AFTER AUTOLOGOUS PERIPHERAL BLOOD STEM CELL TRANSPLANTATION: SINGLE CENTRE EXPERIENCE

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XM02 PLUS CHEMOTHERAPY IS SAFE AND EFFECTIVE IN STEM CELL MOBILIZATION FOR PATIENTS CANDIDATED TO AUTOLOGOUS STEM CELL TRANSPLANTATION

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Fun Sea Factory

Una piastra quadrata incisa da netti solchi d'acqua si popola di forme pure come desunte da un'architettura industriale. Un'industria del divertimento, galleggiante con residenze ricavate da silos, cilindri, cubi, piante centrali, ristoranti, discoteche, spazi comuni. Gli impianti sono a vista su una lunga fettuccia che ci spinge verso il lato est del Porto di Napol

Accumulation of Circulating CCR7+ Natural Killer Cells Marks Melanoma Evolution and Reveals a CCL19-Dependent Metastatic Pathway

none23siImmune checkpoint blockade therapy has changed prognoses for many melanoma patients. However, immune responses that correlate with clinical progression of the disease are still poorly understood. To identify immune responses correlating with melanoma clinical evolution, we analyzed serum cytokines as well as circulating NK and T-cell subpopulations from melanoma patients. The patients' immune profiles suggested that melanoma progression leads to changes in peripheral blood NK and T-cell subsets. Stage IV melanoma was characterized by an increased frequency of CCR7+CD56bright NK cells as well as high serum concentrations of the CCR7 ligand CCL19. CCR7 expression and CCL19 secretion were also observed in melanoma cell lines. The CCR7+ melanoma cell subpopulation coexpressed PD-L1 and Galectin-9 and had stemness properties. Analysis of melanoma-derived cancer stem cells (CSC) showed high CCR7 expression; these CSCs were efficiently recognized and killed by NK cells. An accumulation of CCR7+, PD-L1+, and Galectin-9+ melanoma cells in melanoma metastases was demonstrated ex vivo Altogether, our data identify biomarkers that may mark a CCR7-driven metastatic melanoma pathway.mixedCristiani, Costanza Maria; Turdo, Alice; Ventura, Valeria; Apuzzo, Tiziana; Capone, Mariaelena; Madonna, Gabriele; Mallardo, Domenico; Garofalo, Cinzia; Giovannone, Emilia Dora; Grimaldi, Antonio M; Tallerico, Rossana; Marcenaro, Emanuela; Pesce, Silvia; Zotto, Genny Del; Agosti, Valter; Costanzo, Francesco Saverio; Gulletta, Elio; Rizzo, Aroldo; Moretta, Alessandro; Karre, Klas; Ascierto, Paolo A; Todaro, Matilde; Carbone, EnnioCristiani, Costanza Maria; Turdo, Alice; Ventura, Valeria; Apuzzo, Tiziana; Capone, Mariaelena; Madonna, Gabriele; Mallardo, Domenico; Garofalo, Cinzia; Giovannone, Emilia Dora; Grimaldi, Antonio M; Tallerico, Rossana; Marcenaro, Emanuela; Pesce, Silvia; Zotto, Genny Del; Agosti, Valter; Costanzo, Francesco Saverio; Gulletta, Elio; Rizzo, Aroldo; Moretta, Alessandro; Karre, Klas; Ascierto, Paolo A; Todaro, Matilde; Carbone, Enni

Accumulation of Circulating CCR7+ Natural Killer Cells Marks Melanoma Evolution and Reveals a CCL19-Dependent Metastatic Pathway

Immune checkpoint blockade therapy has changed prognoses for many melanoma patients. However, immune responses that correlate with clinical progression of the disease are still poorly understood. To identify immune responses correlating with melanoma clinical evolution, we analyzed serum cytokines as well as circulating NK and T-cell subpopulations from melanoma patients. The patients' immune profiles suggested that melanoma progression leads to changes in peripheral blood NK and T-cell subsets. Stage IV melanoma was characterized by an increased frequency of CCR7+CD56bright NK cells as well as high serum concentrations of the CCR7 ligand CCL19. CCR7 expression and CCL19 secretion were also observed in melanoma cell lines. The CCR7+ melanoma cell subpopulation coexpressed PD-L1 and Galectin-9 and had stemness properties. Analysis of melanoma-derived cancer stem cells (CSC) showed high CCR7 expression; these CSCs were efficiently recognized and killed by NK cells. An accumulation of CCR7+, PD-L1+, and Galectin-9+ melanoma cells in melanoma metastases was demonstrated ex vivo Altogether, our data identify biomarkers that may mark a CCR7-driven metastatic melanoma pathwa

Haematological immune-related adverse events induced by anti-PD-1 or anti-PD-L1 immunotherapy: a descriptive observational study

Background: Anti-programmed cell death 1 (PD-1) and anti-programmed cell death ligand 1 (PD-L1) antibodies are novel immunotherapies for cancer that can induce immune-related adverse events (irAEs). These adverse events can involve all organs, including the haemopoietic system. Thus far, haematological irAEs (haem-irAEs) have not been extensively characterised. This study aims to provide a comprehensive report of the haem-irAEs induced by anti-PD-1 or anti-PD-L1. Methods: In this descriptive observational study, we included consecutive patients aged at least 18 years with grade 2 or worse haem-irAEs induced by anti-PD-1 or anti-PD-L1 immunotherapy registered in three French pharmacovigilance databases: the Registre des Effets Indésirables Sévères des Anticorps Monoclonaux Immunomodulateurs en Cancérologie (REISAMIC; a prospective registry of patients treated with anti-PD-1 or anti-PD-L1 at a single centre), the ImmunoTOX committee of Gustave Roussy (a national referral database of suspected irAEs in patients treated with immunotherapy), and the registry of the Centre de Référence des Cytopénies Auto-Immunes de l'Adulte (CeReCAI; a national database of autoimmune cytopenias). Cases were reviewed by a central committee; adverse events had to be classed as certainly or probably related to anti-PD-1 or anti-PD-L1 therapy, and their severity was assessed according to the Common Terminology Criteria for Adverse Events (version 4.03). The primary endpoint was clinical description of haem-irAEs, as reported in all databases, and their frequency, as reported in the prospective REISAMIC registry. Findings: We screened 948 patients registered in the three databases from June 27, 2014, to June 29, 2018 (745 from REISAMIC, 190 from the ImmunoTOX committee, and 13 from CeReCAI). 35 patients (21 men and 14 women) with haem-irAEs related to anti-PD-1 or anti-PD-L1 were included in the study. Of 745 patients in the REISAMIC registry treated with anti-PD-1 or anti-PD-L1, four had haem-irAEs, giving a frequency of 0·5%. Median age in the 35 patients was 65 years (IQR 51–75), and the most common tumour types were melanoma (15 [43%] patients), non-small-cell lung cancer (12 [34%] patients), and lymphoma (four [11%] patients). 20 (57%) patients received nivolumab, 14 (40%) received pembrolizumab, and one (3%) received atezolizumab. Among the 35 patients, neutropenia, autoimmune haemolytic anaemia, and immune thrombocytopenia were the most common types of haem-irAE (each in nine patients [26%]), followed by pancytopenia or aplastic anaemia (five patients [14%]), bicytopenia (one patients with thrombocytopenia plus anaemia and one patient with neutropenia plus anaemia [6%]), and pure red cell aplasia (one patient [3%]). The maximum grade of severity was grade 2 in three (9%) patients, grade 3 in five (14%) patients, and grade 4 in 25 (71%) patients; two (6%) patients died from febrile neutropenia during haem-irAE related to anti-PD-1. Haem-irAEs resolved in 21 (60%) of the 35 patients. Interpretation: Haem-irAEs induced by PD-1 or PD-L1 inhibitors are rare but potentially life-threatening events. The most common clinical presentations are neutropenia, autoimmune haemolytic anaemia, immune thrombocytopenia, and aplastic anaemia. Investigations into earlier detection and better management are warranted. Funding: Gustave Roussy and Gustave Roussy Immunotherapy Program.SCOPUS: ar.jDecretOANoAutActifinfo:eu-repo/semantics/publishe