Efficacy and tolerability of anti-programmed death-ligand 1 (PD-L1) antibody (Avelumab) treatment in advanced thymoma

Journal for ImmunoTherapy of Cancer

Kevin Chin¹  Fiona Ginty²  Anup Sood²  Ravi A. Madan³  Geraldine O’Sullivan Coyne³  James L. Gulley³  Andrew L. Mammen⁴  Stefania Pittaluga⁵  Stephen M. Hewitt⁵  Leomar Y. Ballester⁵  Yo-Ting Tsai⁶  Jeffrey Schlom⁶  Renee N. Donahue⁶  Christopher R. Heery⁶  Lauren M. Lepone⁶  Udayan Guha⁷  Susan Perry⁷  Eva Szabo⁷  Anish Thomas⁷  Arun Rajan⁷  Arlene Berman⁷  Raffit Hassan⁷ 

[1] EMD Serono;GE Global Research Center;Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health;Laboratory of Muscle Stem Cells and Gene Regulation, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health;Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health;Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health;Thoracic and Gastrointestinal Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health;

关键词: Thymoma;    Immunotherapy;    Avelumab;    Immune-related adverse events;    Immunosuppressive therapy;    Anti-PD-L1;   

DOI  :  10.1186/s40425-019-0723-9

来源: DOAJ

【 摘 要 】

Abstract 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.

【 授权许可】

Unknown