Molecular predictors of response to pembrolizumab in thymic carcinoma

Cell Rep Med. 2021 Sep 3;2(9):100392. doi: 10.1016/j.xcrm.2021.100392. eCollection 2021 Sep 21.

Abstract

Thymic carcinoma is rare and has a poorer prognosis than thymomas. The treatment options are limited after failure of platinum-based chemotherapy. We previously performed a single-center phase II study of pembrolizumab in patients with advanced thymic carcinoma, showing a 22.5% response rate. Here, we characterize the genomic and transcriptomic profile of thymic carcinoma samples from 10 patients (5 non-responders versus 5 responders) in this cohort, with the main aim of identifying potential predictors of response to immunotherapy. We find that expression of PDL1 and alterations in genes or pathways that correlated with PD-L1 expression (CYLD and BAP1) could be potential predictors for response or resistance to immunotherapy in patients with advanced thymic carcinoma. Our study provides insights into potential predictive markers/pathways to select patients with thymic carcinoma for anti-PD-1 immunotherapy.

Trial registration: ClinicalTrials.gov NCT02364076.

Keywords: immune checkpoint inhibitors; predictors of response; thymic carcinoma; whole exome sequencing; whole-transcriptome sequencing.

Publication types

  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Mutation / genetics
  • Polymorphism, Single Nucleotide / genetics
  • Signal Transduction
  • Thymoma / drug therapy*
  • Thymoma / genetics*
  • Thymoma / immunology
  • Thymus Neoplasms / drug therapy
  • Thymus Neoplasms / genetics*
  • Thymus Neoplasms / immunology
  • Treatment Outcome
  • Tumor Burden / genetics

Substances

  • Antibodies, Monoclonal, Humanized
  • pembrolizumab

Associated data

  • ClinicalTrials.gov/NCT02364076