Absolute Lymphocyte Count Predicts Immune-Related Adverse Events in Patients With Non-Small-Cell Lung Cancer Treated With Nivolumab Monotherapy: A Multicenter Retrospective Study

Abstract

BackgroundAmong patients with advanced non-small-cell lung cancer who were treated with nivolumab monotherapy, the association of peripheral blood count data (at baseline and 2 weeks after treatment initiation) with the early onset of immune-related adverse events (irAEs) and treatment efficacy has not been clearly established. This study aimed to identify peripheral blood count data that may be predictive of the development of nivolumab-induced irAEs in a real-world clinical setting.Materials and MethodsThis multicenter observational study retrospectively evaluated consecutive patients with advanced non-small-cell lung cancer undergoing nivolumab monotherapy in the second- or later-line setting between December 2015 and November 2018 at the National Cancer Center Hospital and Keio University Hospital in Japan. The primary endpoint was the association between peripheral blood count data and irAEs during the 6-week study period. Receiver operating characteristic curve and multivariable logistic regression analyses were performed.ResultsOf the 171 patients evaluated, 73 (42.7%) had ≥1 irAE during the first 6 weeks following treatment initiation. The median time to irAEs from the initiation of nivolumab was 15 (interquartile range: 13–28) days. Receiver operating characteristic curve analyses revealed that the optimal cut-off values of the absolute lymphocyte count, neutrophil-to-lymphocyte ratio, and lymphocyte-to-monocyte ratio 2 weeks after treatment initiation for early irAE onset were 820, 4.3, and 2.2, respectively. In multivariable logistic regression analyses, absolute lymphocyte count >820 at 2 weeks after treatment initiation was significantly associated with an increased risk of early onset of any irAE. In contrast, no significant association was observed for the neutrophil-to-lymphocyte ratio (>4.3) or the lymphocyte-to-monocyte ratio (>2.2) at 2 weeks following treatment initiation.ConclusionsThe absolute lymphocyte count >820 at 2 weeks following nivolumab initiation predicts early onset of irAEs during a 6-week study period. Routinely available absolute lymphocyte count, which is measured after the initiation of nivolumab, may be useful for identifying patients at risk of early onset of irAEs.

Prognostic Value of Baseline Medications Plus Neutrophil-to-Lymphocyte Ratio in the Effectiveness of Nivolumab and Pembrolizumab in Patients With Advanced Non-Small-Cell Lung Cancer: A Retrospective Study

“…Other reasons for choosing a 6-week period included the occurrence rate of irAEs and the timing of computed tomography. The occurrence rate of irAEs was approximately 50% within 6 weeks of ICI treatment ( 26 , 33 ). Imaging evaluations were conducted every 6–8 weeks, starting at treatment initiation.…”

“…This single-center, retrospective observational study was carried out at the National Cancer Center Hospital, a high-volume cancer center in Tokyo, Japan, using data retrieved from electronic medical records. The methodology adopted in this observational study adhered to the STROBE Statement (23) and was the same as that followed in previous studies conducted by our coauthors (24)(25)(26).…”

Blood cell counts can predict adverse events of immune checkpoint inhibitors: A systematic review and meta-analysis

“…Previous treatment was described in four articles ( 15 – 18 ), one of which included previous antitumor regimens as one of the criteria when including patients ( 16 ). Six articles included only patients who received ICI monotherapy ( 15 , 16 , 19 – 22 ). The remaining studies were unrestricted, and they included patients who received ICI in combination with other antitumor treatments.…”

“…A total of 18 studies (11,(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31) were included in the analysis. These studies were published between 2019 to 2022.…”

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“…Other reasons for choosing a 6week period included the occurrence rate of irAEs and the timing of computed tomography. The occurrence rate of irAEs was approximately 50% within 6 weeks of ICI treatment (26,33). Imaging evaluations were conducted every 6-8 weeks, starting at treatment initiation.…”