@article {Rajan269, author = {Arun Rajan and Christopher R. Heery and Anish Thomas and Andrew L. Mammen and Susan Perry and Geraldine O{\textquoteright}Sullivan Coyne and Udayan Guha and Arlene Berman and Eva Szabo and Ravi A. Madan and Leomar Y. Ballester and Stefania Pittaluga and Renee N. Donahue and Yo-Ting Tsai and Lauren M. Lepone and Kevin Chin and Fiona Ginty and Anup Sood and Stephen M. Hewitt and Jeffrey Schlom and Raffit Hassan and James L. Gulley}, title = {Efficacy and tolerability of anti-programmed death-ligand 1 (PD-L1) antibody (Avelumab) treatment in advanced thymoma}, volume = {7}, number = {1}, elocation-id = {269}, year = {2019}, doi = {10.1186/s40425-019-0723-9}, publisher = {BMJ Specialist Journals}, abstract = {Background Thymic epithelial tumors are PD-L1{\textendash}expressing tumors of thymic epithelial origin characterized by varying degrees of lymphocytic infiltration and a predisposition towards development of paraneoplastic autoimmunity. PD-1{\textendash}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{\textendash}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 {\textendash} 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}, URL = {https://jitc.bmj.com/content/7/1/269}, eprint = {https://jitc.bmj.com/content/7/1/269.full.pdf}, journal = {Journal for ImmunoTherapy of Cancer} }