Pre-treatment immune status predicts disease control in NSCLCs treated with chemoradiation and durvalumab.

Abstract

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. 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. 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). Baseline differences in peripheral immune cell populations are associated with disease outcomes in NSCLC patients treated with cCRT and ICI.