Introduction: Durvalumab after concurrent chemoradiation (CCRT) for NSCLC improves survival, but only in a subset of patients. We investigated the effect of severe radiation-induced lymphopenia (sRIL) on survival in these patients.

Methods: Outcomes after CCRT (2010-2019) or CCRT followed by durvalumab (2018-2019) were reviewed. RIL was defined by absolute lymphocyte count (ALC) nadir in samples collected at end of CCRT; sRIL was defined as nadir ALC less than 0.23 × 10/L (the lowest tertile). Progression-free survival (PFS) and overall survival (OS) were calculated by the Kaplan-Meier method. Cox proportional hazard modeling evaluated associations between clinical variables and survival.

Results: Of 309 patients, 192 (62%) received CCRT only and 117 (38%) CCRT plus durvalumab. Multivariable logistic regression analysis indicated that sRIL was associated with planning target volume (OR = 1.002,  = 0.001), stage IIIB disease (OR = 2.77,  = 0.04), and baseline ALC (OR = 0.36, < 0.01). Durvalumab extended median PFS (23.3 versus 14.1 mo,  = 0.003) and OS (not reached versus 30.8 mo, < 0.01). sRIL predicted poorer PFS and OS in both treatment groups. Among patients with sRIL, durvalumab did not improve survival (median = 24.6 mo versus 18.1 mo CCRT only,  = 0.079). On multivariable analyses, sRIL (OR = 1.81, < 0.01) independently predicted poor survival.

Conclusions: Severe RIL compromises survival benefits from durvalumab after CCRT for NSCLC. Measures to mitigate RIL after CCRT may be warranted to enhance the benefit of consolidation durvalumab.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9449658PMC
http://dx.doi.org/10.1016/j.jtocrr.2022.100391DOI Listing

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