Pembrolizumab plus allogeneic NK cells in advanced non–small cell lung cancer patients
Mao Lin, Haihua Luo, Shuzhen Liang, Jibing Chen, Aihua Liu, Lizhi Niu, Yong Jiang
Mao Lin, Haihua Luo, Shuzhen Liang, Jibing Chen, Aihua Liu, Lizhi Niu, Yong Jiang
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Clinical Research and Public Health Immunology

Pembrolizumab plus allogeneic NK cells in advanced non–small cell lung cancer patients

Abstract

BACKGROUND The anti–programmed cell death 1 (anti–PD-1) antibody pembrolizumab is clinically active against non–small cell lung cancer (NSCLC). In addition to T cells, human natural killer (NK) cells, reported to have the potential to prolong the survival of patients with advanced NSCLC, also express PD-1. This study aimed to investigate the safety and efficacy of pembrolizumab plus allogeneic NK cells in patients with previously treated advanced NSCLC.METHODS In total, 109 enrolled patients with a programmed death ligand 1 (PD-L1) tumor proportion score (TPS) of 1% or higher were randomly allocated to group A (n = 55 patients given pembrolizumab plus NK cells) or group B (n = 54 patients given pembrolizumab alone). The patients received i.v. pembrolizumab (10 mg/kg) once every 3 weeks and continued treatment until the occurrence of tumor progression or unacceptable toxicity. The patients in group A continuously received 2 cycles of NK cell therapy as 1 course of treatment.RESULTS In our study, patients in group A had longer survival than did patients in group B (median overall survival [OS]: 15.5 months vs. 13.3 months; median progression-free survival [PFS]: 6.5 months vs. 4.3 months; P < 0.05). In group A patients with a TPS of 50% or higher, the median OS and PFS was significantly longer. Moreover, the patients in group A treated with multiple courses of NK cell infusion had better OS (18.5 months) than did those who received a single course of NK cell infusion (13.5 months).CONCLUSION Pembrolizumab plus NK cell therapy yielded improved survival benefits in patients with previously treated PD-L1+ advanced NSCLC.TRIAL REGISTRATION ClinicalTrials.gov NCT02843204.FUNDING This work was supported by grants from the National Natural Science Foundation of China (NSFC) – Guangdong Joint Foundation of China (no. U1601225); the NSFC (no. 81671965); the Guangdong Provincial Key Laboratory Construction Project of China (no. 2017B030314034); and the Key Scientific and Technological Program of Guangzhou City (no. 201607020016).

Authors

Mao Lin, Haihua Luo, Shuzhen Liang, Jibing Chen, Aihua Liu, Lizhi Niu, Yong Jiang

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Figure 3

Evaluation of immune parameters, tumor markers, and CTCs before treatment and 90 days after treatment.

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Evaluation of immune parameters, tumor markers, and CTCs before treatmen...
(A) Flow cytometric analysis was performed with 6-Color TBNK Reagent to detect lymphocytes in the blood. n = 109. Data are shown as box-and-whisker plots (bottom: 25%; top: 75%; line: median; whiskers: minimum to maximum). Comparison within groups: *P < 0.05 and **P < 0.01, for comparison within groups; #P < 0.05 and ##P < 0.01, for comparison between groups. Statistical significance was determined by 2-sided Student’s t test. (B) Flow cytometric analysis was performed with the Cytometric Bead Array Human Th1/Th2 Cytokine Kit II to detect cytokines in the blood. (C) The levels of tumor markers including CEA, Cyfra21-1, and CA125 were quantitated by chemiluminescence immunoassay. (D) The number of CD45–CK+CD326+ cells (CTCs) was determined with a FACSCanto II. Data are shown as scatter plots with the median and range. n = 109. ‡P < 0.05. ANCOVA was used to analyze the effect of combined treatment on the reduction in CTCs in 7.5 mL of blood compared with pembrolizumab alone.