Abstract
BackgroundThymic 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.MethodsSeven 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.ResultsTwo 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.ConclusionThese 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 registrationClinicalTrials.gov - NCT01772004. Date of registration – January 21, 2013.
Highlights
Thymic epithelial tumors are Programmed death-ligand 1 (PD-L1)–expressing tumors of thymic epithelial origin characterized by varying degrees of lymphocytic infiltration and a predisposition towards development of paraneoplastic autoimmunity
AntiPD-L1 and anti-Programmed death-1 (PD-1) monoclonal antibody (MAb) are fairly well tolerated with a unique adverse event (AE) profile that includes an increased risk for development of immune-related AEs [6, 7]
Resection or biopsy specimens were obtained from 54 patients with the following clinical characteristics: median age 47 years; 35 males/19 females; World Health Organization histology: Thymoma = 19 (AB 1, B1 1, B2 8, B3 8, unclassified thymoma 1), Thymic carcinoma = 35; Masaoka stage: IIB 1, III 1, IVA 16, IVB 36; history of prior systemic therapy in 45 (83%) cases
Summary
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. Thymic epithelial tumors (TETs, consisting of thymomas and thymic carcinomas) arise from epithelial cells of the thymus and have varying degrees of non-neoplastic immature lymphocytic infiltrations [1]. Antibodies targeting PD-1 and PD-L1 are active against various cancers. Among these is avelumab, a fully human anti-PD-L1 IgG1 monoclonal antibody (MAb) that is approved for treatment of Merkel cell carcinoma and urothelial carcinoma. AntiPD-L1 and anti-PD-1 MAbs are fairly well tolerated with a unique adverse event (AE) profile that includes an increased risk for development of immune-related AEs (irAEs) [6, 7]
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call