TY - JOUR
T1 - Severe Radiation-Induced Lymphopenia Attenuates the Benefit of Durvalumab After Concurrent Chemoradiotherapy for NSCLC
AU - Jing, Wang
AU - Xu, Ting
AU - Wu, Lirong
AU - Lopez, Pablo B.
AU - Grassberger, Clemens
AU - Ellsworth, Susannah G.
AU - Mohan, Radhe
AU - Hobbs, Brian P.
AU - Blumenschein, George R.
AU - Tu, Janet
AU - Altan, Mehmet
AU - Lee, Percy
AU - Liao, Zhongxing
AU - Lin, Steven H.
N1 - Publisher Copyright:
© 2022 The Authors
PY - 2022/9
Y1 - 2022/9
N2 - 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 × 109/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, p = 0.001), stage IIIB disease (OR = 2.77, p = 0.04), and baseline ALC (OR = 0.36, p < 0.01). Durvalumab extended median PFS (23.3 versus 14.1 mo, p = 0.003) and OS (not reached versus 30.8 mo, p < 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, p = 0.079). On multivariable analyses, sRIL (OR = 1.81, p < 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.
AB - 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 × 109/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, p = 0.001), stage IIIB disease (OR = 2.77, p = 0.04), and baseline ALC (OR = 0.36, p < 0.01). Durvalumab extended median PFS (23.3 versus 14.1 mo, p = 0.003) and OS (not reached versus 30.8 mo, p < 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, p = 0.079). On multivariable analyses, sRIL (OR = 1.81, p < 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.
KW - Consolidative therapy
KW - Durvalumab
KW - Immunotherapy
KW - Lymphopenia
KW - NSCLC
KW - Radiation
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U2 - 10.1016/j.jtocrr.2022.100391
DO - 10.1016/j.jtocrr.2022.100391
M3 - Article
C2 - 36089921
AN - SCOPUS:85136634171
SN - 2666-3643
VL - 3
JO - JTO Clinical and Research Reports
JF - JTO Clinical and Research Reports
IS - 9
M1 - 100391
ER -