TY - JOUR T1 - Efficacy and tolerability of anti-programmed death-ligand 1 (PD-L1) antibody (Avelumab) treatment in advanced thymoma JF - Journal for ImmunoTherapy of Cancer JO - J Immunother Cancer DO - 10.1186/s40425-019-0723-9 VL - 7 IS - 1 SP - 269 AU - Arun Rajan AU - Christopher R. Heery AU - Anish Thomas AU - Andrew L. Mammen AU - Susan Perry AU - Geraldine O’Sullivan Coyne AU - Udayan Guha AU - Arlene Berman AU - Eva Szabo AU - Ravi A. Madan AU - Leomar Y. Ballester AU - Stefania Pittaluga AU - Renee N. Donahue AU - Yo-Ting Tsai AU - Lauren M. Lepone AU - Kevin Chin AU - Fiona Ginty AU - Anup Sood AU - Stephen M. Hewitt AU - Jeffrey Schlom AU - Raffit Hassan AU - James L. Gulley Y1 - 2019/12/01 UR - http://jitc.bmj.com/content/7/1/269.abstract N2 - Background Thymic epithelial tumors are PD-L1–expressing tumors of thymic epithelial origin characterized by varying degrees of lymphocytic infiltration and a predisposition towards development of paraneoplastic autoimmunity. PD-1–targeting antibodies have been evaluated, largely in patients with thymic carcinoma. We sought to evaluate the efficacy and safety of the anti-PD-L1 antibody, avelumab (MSB0010718C), in patients with relapsed, advanced thymic epithelial tumors and conduct correlative immunological studies.Methods Seven patients with thymoma and one patient with thymic carcinoma were enrolled in a phase I, dose-escalation trial of avelumab (MSB0010718C), and treated with avelumab at doses of 10 mg/kg to 20 mg/kg every 2 weeks until disease progression or development of intolerable side effects. Tissue and blood immunological analyses were conducted.Results Two of seven (29%) patients with thymoma had a confirmed Response Evaluation Criteria in Solid Tumors–defined partial response, two (29%) had an unconfirmed partial response and three patients (two thymoma; one thymic carcinoma) had stable disease (43%). Three of four responses were observed after a single dose of avelumab. All responders developed immune-related adverse events that resolved with immunosuppressive therapy. Only one of four patients without a clinical response developed immune-related adverse events. Responders had a higher absolute lymphocyte count, lower frequencies of B cells, regulatory T cells, conventional dendritic cells, and natural killer cells prior to therapy.Conclusion These results demonstrate anti-tumor activity of PD-L1 inhibition in patients with relapsed thymoma accompanied by a high frequency of immune-related adverse events. Pre-treatment immune cell subset populations differ between responders and non-responders.Trial registration ClinicalTrials.gov - NCT01772004. Date of registration – January 21, 2013.Arun Rajan and Christopher R. Heery contributed equally to this article.Abbreviations:AEAdverse eventALCAbsolute lymphocyte countALTAlanine transaminaseASTAspartate transaminasecDCsConventional dendritic cellsCPKCreatine phosphokinaseCRADACooperative Research and Development AgreementCsACyclosporine ACTCAECommon Terminology Criteria for Adverse EventsCTLCytotoxic T lymphocytesFFPEFormalin-fixed, paraffin-embeddedGIGastrointestinalH&EHematoxylin and eosinICIImmune checkpoint inhibitorsIHCImmunohistochemistryirAEImmune-related adverse eventMAbMonoclonal antibodyMDSCMyeloid derived suppressor cellsMRIMagnetic resonance imagingNCINational Cancer InstituteNKNatural killerPBMCPeripheral blood mononuclear cellsPD-1Programmed death-1PD-L1Programmed death-ligand 1RECISTResponse Evaluation Criteria in Solid TumorsTCRT-cell receptorTETThymic epithelial tumorTregsRegulatory T cells ER -