PD‐L1 expression associated with worse survival outcome in malignant pleural mesothelioma

Abstract

Aim: There is currently a need to identify prognostic biomarkers to assist in a risk adopted approach in treatment of malignant pleural mesothelioma (MPM). Expression of programmed death ligand 1 (PD-L1) has been studied as a prognostic biomarker in a number of tumors given its central role in antitumoral immune response evasion. Four previously published analyses found PD-L1 positivity to be an adverse survival prognostic factor in MPM. This study aims to further investigate the relationship between PD-L1 expression in mesothelioma tissues and survival outcome.Methods: Clinical data of MPM patients from a single institution between 2006 and 2016 were reviewed. Patient's archived tissues were stained with PD-L1 (Clone Ventana SP263). PD-L1 positivity was defined as > 1% membranous staining regardless of intensity.Results: Data from fifty eight patients were analyzed. Median age was 73, majority was male (49, 84%) and had ECOG between 0 and 2 (46, 79%). Most common histopathological subtype was epithelioid (42, 72%), 9 (16%) biphasic subtype and 7 (12%) sarcomatoid. Thirty one patients (53%) received best supportive care and twenty seven patients (47%) received chemotherapy or combination treatment. Forty-two patients had positive PD-L1 expression (72.4%). The median survival time for PD-L1 negative group is 15.5 months and 6 months for the positive group. Positive PD-L1 expression is independently correlated with worse prognosis (HR = 2.02; 95% CI, 1.005-4.057; P-value = 0.0484).Conclusions: Our analysis found a higher percentage of MPM patients with positive PD-L1 (> 1%) compared to other studies. Highly positive PD-L1 expression was associated with statistically significantly lower median survival time.

Gemcitabine Synergizes with Immune Checkpoint Inhibitors and Overcomes Resistance in a Preclinical Model and Mesothelioma Patients

“…Therefore, we first investigated whether gemcitabine influences the expression of PD-L1 by mesothelioma cells in vivo and in vitro. In addition, we found that the expression of PD-L1 is a negative biomarker for survival in mesothelioma, which goes in line with previous studies (14,38) and with data obtained from other tumor entities (39)(40)(41)(42).…”

Clinical Efficacy and Safety of Nivolumab: Results of a Multicenter, Open-label, Single-arm, Japanese Phase II study in Malignant Pleural Mesothelioma (MERIT)

“…It is expressed in the tumors of patients with MPM (12)(13)(14)(15): in 40% of patients with MPM according to one clinical investigation (12) and in 70% according to data from archived patient tissue (13). PD-L1 expression is correlated with a poor prognosis in MPM (12)(13)(14)(15). Nivolumab is a human mAb to the PD-1 receptor that inhibits the interaction between PD-1 and its ligands, PD-L1 or PD-L2.…”

Patient selection for radical surgery for mesothelioma—prognostic factors in a multimodality approach

“…PD-L1 as a novel target for molecular findings with a high interdisciplinary popularity nowadays, may predict the behavior of MPM, and is possibly associated with a lower median survival according to a newly released study by Nguyen et al (49). In this study, a positivity of PD-L1 was associated with a median survival of 6 months compared to survival associated with negative PD-L1 expression of 15.5 months.…”