Original Article
Mesothelioma
Programmed Death 1 Blockade With Nivolumab in Patients With Recurrent Malignant Pleural Mesothelioma

https://doi.org/10.1016/j.jtho.2018.05.038Get rights and content
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Abstract

Introduction

Malignant pleural mesothelioma (MPM) has limited treatment options and a poor outcome. Programmed death 1/programmed death ligand 1 (PD-L1) checkpoint inhibitors have proven efficacious in several cancer types. Nivolumab is a fully humanized monoclonal antibody against programmed death 1 with a favorable toxicity profile. In MPM, the immune system is considered to play an important role. We therefore tested nivolumab in recurrent MPM.

Methods

In this single-center trial, patients with MPM received nivolumab 3 mg/kg intravenously every 2 weeks. Primary endpoint was the disease control rate at 12 weeks. Pre- and on-treatment biopsy specimens were obtained to analyze biomarkers for response.

Results

Of the 34 patients included, 8 patients (24%) had a partial response at 12 weeks and another 8 had stable disease resulting in a disease control rate at 12 weeks of 47%. One reached a partial response at 18 weeks. In 4 patients with stable disease, the tumor remained stable for more than 6 months. Treatment-related adverse events of any grade occurred in 26 patients (76%), most commonly fatigue (29%) and pruritus (15%). Grades 3 and 4 treatment-related adverse events were reported in 9 patients (26%), with pneumonitis, gastrointestinal disorders, and laboratory disorders mostly seen. One treatment-related death was due to pneumonitis and probably initiated by concurrent amiodarone therapy. PD-L1 was expressed on tumor cells in nine samples (27%), but did not correlate with outcome.

Conclusions

Single-agent nivolumab has meaningful clinical efficacy and a manageable safety profile in pre-treated patients with mesothelioma. PD-L1 expression does not predict for response in this population.

Keywords

Mesothelioma
Immunotherapy
Programmed death ligand 1
Nivolumab
Checkpoint inhibitor

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Disclosure: Dr. Quispel-Janssen has received grants from Bristol-Myers Squibb. Dr. Zimmermann has received grants from Bristol-Myers Squibb. Dr. Thunnissen has received personal fees from Histogenex. Dr. Monkhorst has received grants from RocheDx; and has received personal fees from Pfizer, Bristol-Myers Squibb, MSD, RocheDx, and Abbvie. Dr. Schouten has received grants from Bristol-Myers Squibb. Dr. Disselhorst has received grants from Bristol-Myers Squibb. Dr. Burgers has received grants from Bristol-Myers Squibb; and has received personal fees from Boehringer, Roche, and Astra Zeneca. Dr. Buikhuisen has received grants from Bristol-Myers Squibb. Dr. Baas has received grants from Bristol-Myers Squibb and MSD; and has received personal fees from Bristol-Myers Squibb, MSD, Astra Zeneca, and Targovax. The remaining authors declare no conflict of interest.