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

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.

Association Between Immune-Related Adverse Events and Clinical Efficacy in Patients with Melanoma Treated With Nivolumab: A Multicenter Retrospective Study

“…Previous studies have also found that increases in peripheral lymphocyte count after nivolumab treatment are associated with better clinical response in patients with lung cancer and melanoma. 22,23 The interaction of PD-1 with PD-L1 prevents the activation and proliferation of T cells. Inhibition of PD-L1 binding with PD-1 induces T-cell activation in the priming phase and increases the number of cytotoxic T cells.…”

“…Inhibition of PD-L1 binding with PD-1 induces T-cell activation in the priming phase and increases the number of cytotoxic T cells. 24 Diehl et al 22 reported that lymphocytopenia affected progression-free revival in patients receiving immune checkpoint inhibitor, which may be related to antitumor T-cell dysfunction resulting from immune exhaustion and depletion. These results indicate that the increase in the number of peripheral lymphocytes may be related to enhancement in the antitumor effect and occurrence of irAEs induced by nivolumab.…”

Multiparameter Flow Cytometry Assay for Quantification of Immune Cell Subsets, PD‐1 Expression Levels and PD‐1 Receptor Occupancy by Nivolumab and Pembrolizumab

“…Approved biomarkers include PD-L1 expression and mismatch repair deficient/microsatellite instability high tumors (14,15). Furthermore, absolute lymphocyte and monocyte counts have shown to predict time to reponse, time to progression, overall survival, and immune related adverse effects of immunotherapy (21,22). Furthermore, absolute lymphocyte and monocyte counts have shown to predict time to reponse, time to progression, overall survival, and immune related adverse effects of immunotherapy (21,22).…”

“…Other biomarkers correlating to response include tumor-infiltrating lymphocytes, number of CD8 + -Tcells, T-cell receptor clonality, and IFN-γ signature expression (16)(17)(18)(19)(20). Furthermore, absolute lymphocyte and monocyte counts have shown to predict time to reponse, time to progression, overall survival, and immune related adverse effects of immunotherapy (21,22).…”

Favorable response to nivolumab in a young adult patient with metastatic histiocytic sarcoma

“…After 2 months of nivolumab treatment, a PET‐CT scan showed worsening metastatic disease in the left femoral neck and bilateral lungs (Supporting Information Figure 1C). Nivolumab treatment was continued despite apparent progression, since her persistent lymphopenia offered an explanation for her lackluster response . Although pseudoprogression may have contributed to the increased size of some preexisting sites of metastatic disease, it was thought to more likely represent true progression based on the presence of new disease and her overall immunosuppressed state.…”