Abstract
BACKGROUND: The impact of peripheral blood immune measures and radiation-induced lymphopenia on outcomes in non-small cell lung cancer (NSCLC) patients treated with concurrent chemoradiation (cCRT) and immune check point inhibition (ICI) has yet to be fully defined. METHODS: Stage III NSCLC patients treated with cCRT and ≥1 dose of durvalumab across a cancer center were examined. Peripheral blood counts were assessed pre-cCRT, during cCRT and at the start of ICI. These measures and risk-scores from two published models estimating radiation dose to immune-bearing organs were tested for association with disease control. RESULTS: We assessed 113 patients treated with cCRT and a median of 8.5 months of durvalumab. Median PFS was 29 months (95% CI 18-35 months). A lower pre-cCRT ALC (HR: 0.51 (95% CI: 0.32-0.82), p = 0.02) and a higher pre-cCRT ANC (HR: 1.14 (1.06-1.23), p = 0.005) were associated with poor PFS. Neither ALC nadir, ALC at ICI start, ANC at ICI start or the normalized change in ALC from pre-cCRT to nadir were significantly associated with PFS (p = 0.07-0.49). Also, risk scores from the two radiation-dose models were not associated with PFS (p = 0.14, p = 0.21) but were so with the ALC Nadir (p = 0.001, p = 0.002). A higher pre-cCRT NLR was the strongest predictor for PFS (HR: 1.09 (1.05-1.14), p = 0.0001). The 12-month PFS in patients with the bottom vs. top NLR tertile was 84% vs 46% (p = 0.000004). CONCLUSIONS: Baseline differences in peripheral immune cell populations are associated with disease outcomes in NSCLC patients treated with cCRT and ICI.