Use of targeted next generation sequencing to characterize tumor mutational burden and efficacy of immune checkpoint inhibition in small cell lung ... - PubMed - NCBI

Use of targeted next generation sequencing to characterize tumor mutational burden and efficacy of immune checkpoint inhibition in small cell lung ... - PubMed - NCBI

J Immunother Cancer. 2019 Mar 28;7(1):87. doi: 10.1186/s40425-019-0572-6.

Use of targeted next generation sequencing to characterize tumor mutational burden and efficacy of immune checkpoint inhibition in small cell lung cancer.

Ricciuti B1, Kravets S2, Dahlberg SE2, Umeton R3,4, Albayrak A3, Subegdjo SJ1, Johnson BE1, Nishino M5, Sholl LM6, Awad MM7.

Author information

Abstract

BACKGROUND:

Clinically-available biomarkers to identify the fraction of patients with small cell lung cancer (SCLC) who respond to immune-checkpoint inhibitors (ICIs) are lacking. High nonsynonymous tumor mutational burden (TMB), as assessed by whole exome sequencing, correlates with improved clinical outcomes for patients with SCLC treated with ICIs. Whether TMB as assessed by targeted next generation sequencing (NGS) is associated with improved efficacy of ICIs in patients with SCLC is currently unknown. Here we determined whether TMB by targeted NGS is associated with efficacy of ICIs in patients with SCLC.

METHODS:

We collected clinicopathologic data from patients with relapsed or refractory SCLC which underwent targeted NGS with TMB assessment by the Dana-Farber Cancer Institute OncoPanel platform. The relationship between TMB and clinical outcomes after treatment with ICIs was investigated.

RESULTS:

Among the 52 patients treated with ICIs, we found no significant difference in the objective response rate (ORR) between patients with a TMB above the 50th percentile ("TMB high") and those with a TMB at or below the 50th percentile ("TMB low"). The median progression-free survival (mPFS) and median overall survival (mOS) were significantly longer in patients with a high TMB compared to those with a low TMB (mPFS: 3.3 versus 1.2 months, HR: 0.37 [95% CI: 0.20-0.69], P < 0.01; mOS: 10.4 versus 2.5 months, HR: 0.38 [95% CI: 0.19-0.77], P < 0.01). The one-year PFS and OS rates improved with increasing mutational load when TMB was divided into tertiles.

CONCLUSIONS:

These findings show that targeted NGS, a readily available clinical diagnostic test, can be used to identify patients with SCLC who are most likely to benefit from treatment with immune checkpoint inhibitors.

KEYWORDS:

Immunotherapy; SCLC; Tumor mutational burden

PMID:

 

30922388

 

DOI:

 

10.1186/s40425-019-0572-6

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