Genomic characterization of malignant pleural mesothelioma and associated clinical outcomes

Paul Markowitz, Malini Patel, Roman Groisberg, Joseph Aisner, Salma K. Jabbour, Subhajyoti De, Shridar Ganesan, Jyoti Malhotra

Research output: Contribution to journalArticlepeer-review

Abstract

Introduction: Malignant pleural mesothelioma (MPM) is a rare malignancy with a poor prognosis. While treatment with a platinum-based chemotherapy is the standard of care, many patients have rapid progression of disease with a median overall survival of ~12 months. Limited data exist about the genomic alterations associated with MPM and their clinical implications. Methods: We report genomic alterations and clinical data for 17 patients with MPM who had next generation sequencing performed. Overall survival (OS) and progression-free survival (PFS) were analyzed with Kaplan-Meier method. Results: Median age at diagnosis was 70 years (range 55–85), and 47% of the patients were male. The most common genomic alterations in the 17 patients were NF2 (53%), BAP1 (41%), CDKN2A (41%) and TP53 (29%). The median OS was 10.8 months. When stratified by mutational status, patients had better median OS if they had a BAP1 alteration compared to TP53 alteration (median OS 14.5 vs 7.2 months). Median PFS with first-line chemotherapy was 7 months (SD ± 3.3). However, patients with TP53 mutations had worse PFS with chemotherapy with median of only 3.9 months. Tumor mutation burden (TMB) was available for 12 patients and all had low TMB (range 1 to 8.1 mutation/Mb). Median PFS with immunotherapy was poor with at 1.5 months (SD ±0.4) and there was no significant difference in PFS with immunotherapy based on molecular profile. Conclusion: Our study has identified that TP53 confers worse survival and response to platinum chemotherapy compared to BAP1. Overall PDL1 expression and TMB is low in patients with MPM resulting in limited benefit from single agent PD-1/PD-L1 agent.

Original languageEnglish (US)
Article number100232
JournalCancer Treatment and Research Communications
Volume25
DOIs
StatePublished - Jan 2020

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Keywords

  • Genomic
  • Mesothelioma
  • Mutation burden

Fingerprint Dive into the research topics of 'Genomic characterization of malignant pleural mesothelioma and associated clinical outcomes'. Together they form a unique fingerprint.

Cite this