Associations between longitudinal pretreatment BMI and neutrophil/lymphocyte ratio(NLR) and progression-free(PFS) and overall survival(OS) in advanced NSCLC patients treated with single agent anti-PD-1/anti-PDL1 monoclonal antibodies(mAbs).

Abstract

e21189 Background: Several parameters that have been associated with outcomes in patients with metastatic NSCLC treated with anti-PD1/PDL1 mAbs include tumor PD-L1 expression, tumor mutational burden, and baseline NLR. Further investigation into clinical correlates of benefit with immune checkpoint inhibitors remains an unmet need. Methods: The objective of this retrospective study was to examine the potential influence of pretreatment cachexia and chronic inflammation in patients with NSCLC that received second- or third- line single agent anti-PD1/PDL1 mAbs. Weight, BMI, and NLR, as well as longitudinal changes in these variables from at least six-weeks prior to initiation of treatment were correlated with progression-free and overall survival (PFS/OS). These associations were assessed using statistical methods for time-to-event analysis. Results: 192 patients were included: 59% female, 72% Caucasian, 18% African American, 79% current or former smokers. 185 patients had pretreatment NLR values and 63% and 42% had NLR ratios > 3.5 and > 5, respectively. 187 patients had pretreatment weight and BMI available. Of these, 63% had a loss in BMI prior to initiation of anti-PD1/PDL1 mAbs, 29% with > 5% loss. Any BMI loss as well as BMI loss > 5% over the time period prior to treatment initiation were associated with shorter PFS (p < 0.01, 2.1 vs 4.37 mos for loss > 5% vs ≤ 5%) and change in BMI assessed in continuous scale was also associated with PFS (HR = 0.94, p < 0.05). Similarly, any BMI loss and BMI loss > 5% were associated with shorter OS (p < 0.01. 7.33 vs 12.23 mos for loss > 5% vs ≤ 5%) and change in BMI and baseline BMI assessed in continuous scale were additionally associated with OS (HR = 0.97 and 0.94, p < 0.05). Baseline NLR > 5 was associated with shorter PFS (p < 0.01) and baseline NLR assessed in continuous scale was negatively associated (HR = 1.01, p < 0.05). Moreover, pre-treatment NLR > 5 and baseline NLR > 3.5 were associated with shorter OS (p < 0.05). Pre-treatment NLR, baseline NLR, and %change in NLR, assessed in continuous scale, were negatively associated with OS (HR = 1.04, 1.02, 1.12, p < 0.01). Conclusions: This retrospective study identified clinical features of NLR and BMI at treatment initiation and in the immediate pre-treatment period that were associated with PFS and OS on anti-PD1/PDL1 mAbs therapy. These parameters can easily be investigated in the front-line population. They may also have utility in identifying patients that would benefit from therapeutic strategies to reverse weight loss and inhibit immunosuppressive effects associated with elevated NLR in order to increase the effectiveness of immunotherapy.