296 Immune correlates of clinical response to Avelumab in patients with advanced thymic epithelial tumors. (10th December 2020)

• Record Type: Journal Article
• Authors: Tsai, Yo-Ting; Rajan, Arun; Gulley, James; Schlom, Jeffrey; Donahue, Renee
• Is Part Of: Journal for immunotherapy of cancer. Volume 8(2020)Supplement 3
• Page Start: A181
• Page End: A181
• Publication Date: 2020-12-10
• Subjects: Cancer -- Immunotherapy -- Periodicals; Cancer -- Immunological aspects -- Periodicals; Tumors -- Immunological aspects -- Periodicals; Immunotherapy -- Periodicals; 616.99406105
• DOI: 10.1136/jitc-2020-SITC2020.0296
• Languages: English
• ISSNs: 2051-1426

Abstract

Abstract : Background: Thymic epithelial tumors (TET), consisting of thymomas and thymic carcinomas, are PD-L1-expressing tumors characterized by varying degrees of lymphocytic infiltration and a predisposition towards the development of paraneoplastic autoimmunity. As part of a phase I study (NCT01772004 ), the anti-tumor activity of patients with relapsed, advanced TET to avelumab (anti-PD-L1), was demonstrated and was accompanied by a high frequency of immune related adverse events (irAE). The current study aimed to identify immune related signatures that associate with clinical response and/or the development of irAE. Methods: Eight patients with recurrent TET were 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. Peripheral blood mononuclear cells (PBMC) were obtained before and during therapy, and interrogated by multicolor flow cytometry to evaluate 123 immune subsets, as well as by T-cell receptor (TCR) sequencing to evaluate TCR diversity. Results: Four of 8 TET patients had partial responses and 3 had stable disease. All responders developed irAEs that resolved with immunosuppressive therapy, compared to only 1 of 4 non responders. Analyses of PBMC subsets prior to therapy showed that responders had higher absolute lymphocyte counts, and lower frequencies of B cells, Tregs, conventional dendritic cells (cDCs), and NK cells, compared to non-responders. There was also a trend towards a higher level of TCR diversity in those patients who subsequently had a radiological response and developed irAE. Conclusions: Immune profiling identified specific immune measures prior to therapy that differed between responders and non-responders, that may serve as predictive biomarkers to identify patients with relapsed TET most likely to benefit from avelumab and/or to develop irAE. Trial Registration: NCT01772004 Ethics Approval: All patients provided written informed consent for participation in a clinical trial that was approved by the Institutional Review Board at the National Cancer Institute (NCT01772004 ).