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Multicenter Study
. 2022 Feb;71(2):461-471.
doi: 10.1007/s00262-021-03000-8. Epub 2021 Jul 7.

Pre-pembrolizumab neutrophil-to-lymphocyte ratio (NLR) predicts the efficacy of second-line pembrolizumab treatment in urothelial cancer regardless of the pre-chemo NLR

Takashi Kobayashi  1 , Katsuhiro Ito  2 , Takahiro Kojima  3 , Satoru Maruyama  4 , Shoichiro Mukai  5 , Masakazu Tsutsumi  6 , Jun Miki  7 , Tomoya Okuno  8 , Yuko Yoshio  9 , Hiroaki Matsumoto  10 , Toru Shimazui  11 , Takehiko Segawa  12 , Takashi Karashima  13 , Kimihiko Masui  14 , Fumimasa Fukuta  15 , Kojiro Tashiro  16 , Kazuto Imai  17 , Shigetaka Suekane  18 , Seiji Nagasawa  19 , Shin Higashi  20 , Tomohiro Fukui  21 , Osamu Ogawa  22 , Hiroshi Kitamura  23 , Hiroyuki Nishiyama  3
Affiliations
Multicenter Study

Pre-pembrolizumab neutrophil-to-lymphocyte ratio (NLR) predicts the efficacy of second-line pembrolizumab treatment in urothelial cancer regardless of the pre-chemo NLR

Takashi Kobayashi et al. Cancer Immunol Immunother. 2022 Feb.

Abstract

Neutrophil-to-lymphocyte ratio (NLR) was reported to be associated with prognosis of urothelial cancer (UC) patients receiving systemic chemotherapy or immunotherapy. However, it has not been elucidated how preceding first-line chemotherapy affects NLR and subsequent second-line pembrolizumab treatment. This multicenter study analyzed 458 patients with metastatic UC who received first-line chemotherapy and second-line pembrolizumab with regard to pre-chemotherapy and pre-pembrolizumab NLR in association with the efficacy of chemotherapy and pembrolizumab treatment. NLR was increased in 47% while decreased in 53% of patients before and after first-line chemotherapy. High pre-chemotherapy NLR (≥ 3) was significantly associated with unfavorable overall (OS, P = 0.0001) and progression-free (P < 0.0001) survivals after first-line chemotherapy. However, pre-chemotherapy NLR showed only modest influence on radiological response and survival after second-line pembrolizumab treatment, whereas pre-pembrolizumab NLR showed higher association. NLR decrease was associated with partial response or greater objective response by first-line chemotherapy, while NLR increase was associated with higher patient age. In conclusion, immediate pre-chemotherapy and pre-pembrolizumab NLR was significantly associated with efficacy of the following treatment, respectively. However, even patients with high pre-chemotherapy NLR achieved favorable OS if they had their NLR reduced by chemotherapy, whereas those with high pre-chemotherapy NLR yielded unfavorable OS if they had their NLR remained high after chemotherapy, suggesting that chemotherapy may have differential effect on the efficacy of subsequent pembrolizumab treatment in UC patients.

Keywords: Chemotherapy; Metastatic urothelial cancer; Overall survival; Pembrolizumab; Progression-free survival.

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
a Chart of NLR values at the pre-chemotherapy (pre-chemo) and pre-pembrolizumab (pre-pembro) settings. b Histogram chart of change in neutrophil-to-lymphocyte ratio (NLR). c Sankey diagraMDepicting change in NLR from pre-chemotherapy to pre-pembrolizumab settings. High NLR was defined as ≥ 3
Fig. 2
Fig. 2
Kaplan–Meier plots displaying survival of 458 patients. a, b Overall a and progression-free b survivals from the initiation of first-line chemotherapy (CTx) with regard to pre-chemotherapy NLR
Fig. 3
Fig. 3
a Overall survival from the initiation of second-line pembrolizumab with regard to pre-chemotherapy NLR. High NLR was defined as ≥ 3. b Overall survival from the initiation of second-line pembrolizumab with regard to pre-pembrolizumab NLR. c, d Mosaic charts for the proportion of best objective response to pembrolizumab treatment with regard to pre-chemotherapy c and pre-pembrolizumab d NLR. High NLR was defined as ≥ 3
Fig. 4
Fig. 4
a Kaplan–Meier plots displaying overall survival of 230 patients with pre-chemotherapy NLR ≥ 3 from the initiation of first-line chemotherapy (CTx) with regard to pre-pembrolizumab NLR. b Kaplan–Meier plots displaying overall survival of 228 patients with pre-chemotherapy NLR < 3 from the initiation of first-line chemotherapy (CTx) with regard to pre-pembrolizumab NLR. High NLR was defined as ≥ 3
See this image and copyright information in PMC

References

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