High baseline lymphocyte count is a predictive biomarker of prolonged time to progression in patients with advanced solid tumors receiving checkpoint inhibitors.

Abstract

e14532 Background: Biomarkers predicting response to checkpoint inhibitor are needed to better select patients most likely to benefit from treatment. We observed that baseline absolute lymphocyte count (ALC) can predict durable responses to anti-PD-1 antibodies in various malignancies. Methods: This is a retrospective analysis of patients with advanced solid tumors treated with anti-PD-1 antibodies. Pembrolizumab was given at 2 mg/kg every 3 weeks, Nivolumab at 3 mg/kg every 2 weeks. Peripheral ALC and absolute neutrophil count (ANC) from routine safety labs were collected at baseline, cycle 4 and cycle 8. Evaluation of response was based on irRECIST. Neutrophil lymphocyte ratio [NLR = ANC/ALC] was stratified by ≤4 or > 4. The lymphocyte count cutoff was 1000/mm3. Time to progression (TTP) and overall survival (OS) were estimated with the Kaplan-Meier method. Differences between groups were estimated with the log rank test. Results: We have retrospectively evaluated 40 patients with unresectable stage III/IV Non Small Cell Lung Cancer (squamous n. 17; 42.5%, adenocarcinoma n. 7; 17.5%), Malignant Melanoma (n.11; 27.5%), Renal Cell Carcinoma (n.5; 12.5%) treated with anti-PD-1 antibodies. 6 pts (15%) received treatment as 1st line, 14 pts (35%) as 2nd line, 20 pts (15%) as ≥ 3rd line. We observed a 29% partial response (PR), 31% stable disease (SD) and 40% progressive disease (PD). The overall response rate (ORR) was 29% [I.C. 95% 13-42]. Median TTP was 5.5 months [IC 95% 3.3-NR]. Median OS was not reached. Pts with baseline ALC ≥1000/mm3 had significantly longer TTP (median value not reached), compared with those who had ALC < 1000/mm3 (median TTP 2.8 months), p = 0.01. There was also a trend for longer TTP in patients with NLR < 4 vs ≥4 (4.9 vs 10.5 months, p 0.44). Conclusions: In our observation baseline ALC ≥1000/mm3 is a predictive biomarker of prolonged TTP in patients treated with anti-PD-1 antibodies. The potential predictive value of this test should be prospectively validated.

Lymphopenia as a Potential Predictor of Ipsilateral Breast Tumor Recurrence in Early Breast Cancer

“…Past reports have suggested that pretreatment lymphopenia in patients with advanced cancers is a prognostic factor for survival, which supports the conclusion that tumor-induced lymphopenia, preexisting immunosuppressive conditions, or combinations of both factors lead to poor clinical outcome (16). Recent reports regarding poor responses to immune checkpoint inhibitors in patients with lymphopenia support the conclusion that both factors may be associated with treatment results (17,18). Therefore, in EBC patients for whom complete tumor resection is expected, it may be appropriate to evaluate the clinical impact of innate lymphopenia and the ability to overcome this condition.…”

Predictive value of peripheral lymphocyte counts for immune checkpoint inhibitor efficacy in advanced head and neck squamous cell carcinoma

“…Several studies have previously assessed the predictive value of various peripheral lymphocyte measures for ICI therapy response, including absolute or relative lymphocyte count at the beginning of treatment, on-treatment, or dynamic changes during treatment. High baseline ALC and increase in ALC during the treatment were associated with better response to anti-PD-1/PD-L1 therapy (4,6,7). Similarly, low NLR and decrease in NLR with anti-PD-1 blockade were associated with improved outcomes in various solid tumors (5,8,9).…”