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

J Immunother Cancer. 2019 Oct 21;7(1):269. doi: 10.1186/s40425-019-0723-9.

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.

Keywords: Anti-PD-L1; Avelumab; Immune-related adverse events; Immunosuppressive therapy; Immunotherapy; Thymoma.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Antineoplastic Agents, Immunological / administration & dosage
  • Antineoplastic Agents, Immunological / adverse effects
  • Antineoplastic Agents, Immunological / therapeutic use*
  • B7-H1 Antigen / antagonists & inhibitors*
  • Biomarkers
  • Biomarkers, Tumor
  • Female
  • Gene Expression Profiling
  • Humans
  • Immunohistochemistry
  • Immunophenotyping
  • Male
  • Middle Aged
  • Molecular Targeted Therapy
  • Neoplasm Staging
  • Thymoma / diagnosis
  • Thymoma / drug therapy*
  • Thymoma / etiology
  • Thymoma / mortality
  • Thymus Neoplasms / diagnosis
  • Thymus Neoplasms / drug therapy*
  • Thymus Neoplasms / etiology
  • Thymus Neoplasms / mortality
  • Tomography, X-Ray Computed
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents, Immunological
  • B7-H1 Antigen
  • Biomarkers
  • Biomarkers, Tumor
  • CD274 protein, human
  • avelumab

Associated data

  • ClinicalTrials.gov/NCT01772004