Case Report: A Rare Case of Metachronous Multiple Primary Lung Cancers in a Patient With Successful Management by Switching From Anti-PD-1 Therapy to Anti-PD-L1 Therapy

Front Immunol. 2021 Jun 2:12:683202. doi: 10.3389/fimmu.2021.683202. eCollection 2021.

Abstract

Without global standard diagnostic criteria, distinguishing multiple primary lung cancers (MPLCs) from intrapulmonary metastasis or histologic transformation has been a big challenge in clinical practice. Here, we described a rare case of metachronous adenocarcinoma and small cell lung cancer (SCLC) in a patient who developed drug resistance to pembrolizumab. Both DNA-sequencing and RNA-sequencing were performed on primary adenocarcinoma and resistant lesions. Through the comparison of primary adenocarcinoma and novel lesion mutation profiles, along with bioinformatic estimation of immune proportion by using RNA sequence data, we revealed the origin and tumor microenvironment of the two lesions. No shared mutations were detected between lung adenocarcinoma (LUAD) and SCLC from the same patient, suggesting these two lesions might be from separate primary lung cancers. Compared to LUAD, SCLC showed a relatively cold microenvironment, including negative PD-L1. The patient obtained durable clinical benefits upon treatment with atezolizumab, without experiencing immune-related adverse events. Disease progression should be monitored with prompt re-biopsy and molecular profiling to spot a potential histologic change and to shed light on therapeutic alternatives. The use of atezolizumab, either alone or in combination with other agents, may be a potential therapeutic strategy for patients with both LUAD and SCLC.

Keywords: immunotherapy; metachronous multiple primary lung cancer (mMPLC); next-generation sequencing (NGS); re-biopsy; resistance.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged, 80 and over
  • B7-H1 Antigen / antagonists & inhibitors*
  • Biomarkers, Tumor / antagonists & inhibitors*
  • Drug Substitution*
  • Female
  • Humans
  • Immune Checkpoint Inhibitors / administration & dosage
  • Immune Checkpoint Inhibitors / adverse effects
  • Immune Checkpoint Inhibitors / therapeutic use*
  • Immunohistochemistry
  • Molecular Targeted Therapy*
  • Neoplasms, Multiple Primary / diagnosis*
  • Neoplasms, Multiple Primary / drug therapy*
  • Neoplasms, Multiple Primary / etiology
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors
  • Symptom Assessment
  • Tomography, X-Ray Computed
  • Treatment Outcome

Substances

  • B7-H1 Antigen
  • Biomarkers, Tumor
  • CD274 protein, human
  • Immune Checkpoint Inhibitors
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor