Survival impact of lymphocytopenia during chemoradiation in locally advanced NSCLC patients treated with adjuvant durvalumab.

Abstract

8054 Background: Adjuvant durvalumab has transformed the treatment landscape for patients with locally advanced non-small cell lung cancer (NSCLC) following concurrent chemoradiotherapy (CRT). However, in the landmark PACIFIC trial, only one-third of patients achieved long-term disease-free survival, underscoring the need for additional biomarkers to guide patient selection. Lymphocytopenia, a common side effect of CRT, has been associated with poor responses to immunotherapy. In this study, we investigate the incidence, degree, and timing of CRT-induced lymphocytopenia and association with survival among patients receiving durvalumab adjuvant therapy. Methods: This retrospective study included patients with unresectable Stage III NSCLC who underwent CRT followed by at least one dose of durvalumab at The Ohio State University. Clinical data was extracted through review of electronic medical records. Absolute lymphocyte count (ALC) was collected at baseline prior to CRT initiation, the lowest ALC during CRT, and 30 days post-CRT. Lymphocytopenia was classified using the Common Terminology Criteria for Adverse Events V5. Overall survival (OS) was calculated from CRT initiation to date of death or loss to follow-up. Cox proportional hazards model was used to evaluate the associations of baseline, lowest, post-CRT ALC, as well as the percentage change in ALC from baseline to lowest (relative ALC change) with OS. Results: This study included 118 patients with a mean age of 63.9 years (SD: 9.7), who received durvalumab within 12 weeks of completing CRT. Baseline characteristics were obtained (Table 1). Median baseline ALC was 1645 cells/µL (IQR: 1340–2190), dropping to 300 cells/µL (IQR: 200–450) during CRT and 755 cells/µL (IQR: 510–1040) post-CRT. Grade ≥3 lymphocytopenia occurred in 97 patients (82.2%) during CRT. Baseline, lowest, and post-CRT ALC were not associated with OS, but the relative decline in ALC from baseline was strongly associated. A 10% decrease in ALC from baseline was associated with a 48% increased risk of death (HR = 1.48; 95% CI: 1.14–1.91; p < 0.01) after adjusting for age, ECOG performance status (PS), histology, PD-L1 expression, chemotherapy regimen, and RT duration. Conclusions: Dynamic change in ALC from pre-treatment baseline to nadir during CRT is a strong prognostic indicator for OS in patients with advanced NSCLC receiving adjuvant durvalumab. Studies are warranted to elucidate the underlying mechanisms. Additionally, this highlights lymphocytopenia as a potentially modifiable side effect, which could be addressed with myeloprotective treatment. Baseline characteristics. Characteristic No. of Patients (%) ECOG PS = 0 18 (15.4) ECOG PS = 1 80 (68.4) Positive PD-L1 expression 80 (76.9) Squamous cell vs. other 51 (43.2); 67 (56.8) Weekly carboplatin/paclitaxel vs. other 88 (74.6); 30 (25.4)