Oncotarget

Research Papers:

Relationships between lymphocyte counts and treatment-related toxicities and clinical responses in patients with solid tumors treated with PD-1 checkpoint inhibitors

Adam Diehl, Mark Yarchoan, Alex Hopkins, Elizabeth Jaffee and Stuart A. Grossman _

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Oncotarget. 2017; 8:114268-114280. https://doi.org/10.18632/oncotarget.23217

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Abstract

Adam Diehl1, Mark Yarchoan2, Alex Hopkins2, Elizabeth Jaffee2 and Stuart A. Grossman2

1Department of Medicine at The Johns Hopkins Hospital, Baltimore, MD, USA

2The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA

Correspondence to:

Stuart A. Grossman, email: grossman@jhmi.edu

Keywords: lymphopenia; PD-1 inhibitor; response; immune-related adverse event; radiation

Received: July 27, 2017    Accepted: November 28, 2017    Published: December 14, 2017

ABSTRACT

The relationships between absolute lymphocyte counts (ALC), drug- related toxicities, and clinical responses remain unclear in cancer patients treated with PD-1 (programmed cell death 1) inhibitors. We performed a retrospective review of 167 adult solid tumor patients treated with nivolumab or pembrolizumab at a single institution between January 2015 and November 2016. Patients with an ALC >2000 at baseline had an increased risk of irAE (OR 1.996, p<0.05) on multivariate analysis. In a multivariate proportional hazards model, a shorter time to progression was noted in patients who were lymphopenic at baseline (HR 1.45 (p<0.05)) and at three months (HR 2.01 (p<0.05)). Patients with baseline lymphopenia and persistent lymphopenia at month 3 had a shorter time to progression compared to those who had baseline lymphopenia but recovered with ALC > 1000 at 3 months (HR 2.76, p<0.05). Prior radiation therapy was the characteristic most strongly associated with lymphopenia at 3 months (OR 2.24, p<0.001). These data suggest that patients with higher baseline lymphocyte counts have a greater risk for irAE, whereas patients with lymphopenia at baseline and persistent lymphopenia while on therapy have a shorter time to progression on these agents. These associations require further validation in additional patient cohorts.


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