Pretreatment Eosinophil Counts in Patients With Advanced or Metastatic Urothelial Carcinoma Treated With Anti-PD-1/PD-L1 Checkpoint Inhibitors

Mota, José Maurício; Teo, Min Yuen; Whiting, Karissa; Li, Han A; Regazzi, Ashely M; Lee, Chung-Han; Funt, Samuel A.; Bajorin, Dean F.; Ostrovnaya, Irina; Iyer, Gopa; Rosenberg, Jonathan E.

doi:10.1097/cji.0000000000000372

Cited by 10 publications

(22 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…An early increase in the peripheral eosinophil count at weeks 2 or 3 was observed, but changes in eosinophil counts at weeks 2 or 3 and 6 were not clearly associated with outcomes. 22 The present study did not show that the pretreatment REC (REC ≥4.8% and <4.8%) was associated with a significant difference in the OS (p=0.997), but posttreatment changes, namely an increased REC at 3 weeks after pembrolizumab, were an independent prognostic factor (P=0.002). Several factors, such as the sample size, kind of ICI, timing of the eosinophil count and the cut-off value of eosinophils, might be responsible for the discrepant clinical outcomes between the present and previous studies.…”

Section: Discussioncontrasting

confidence: 88%

“… 19–21 Recently, eosinophils were shown to be associated with the efficacy of ICIs in melanoma, 8 lung cancer, 9 renal cell carcinoma (RCC) 10 and UC. 22 In UC, it was reported that a low pretreatment eosinophil count (<100 cells/μL) was associated with poorer outcomes following treatment with ICIs than a higher count. An early increase in the peripheral eosinophil count at weeks 2 or 3 was observed, but changes in eosinophil counts at weeks 2 or 3 and 6 were not clearly associated with outcomes.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

The Association of Clinical Outcomes with Posttreatment Changes in the Relative Eosinophil Counts and Neutrophil-to-Eosinophil Ratio in Patients with Advanced Urothelial Carcinoma Treated with Pembrolizumab

Furubayashi

Minato

Negishi

et al. 2021

CMAR

View full text Add to dashboard Cite

Background To evaluate the association of clinical outcomes with posttreatment changes in the relative eosinophil count (REC) and neutrophil-to-eosinophil ratio (NER) in patients with advanced urothelial cancer (UC) treated with pembrolizumab. Materials and Methods We retrospectively analyzed 105 patients with advanced UC who received pembrolizumab after the failure of platinum-based chemotherapy. The REC and NER before and three weeks after pembrolizumab were recorded. A receiver operating characteristic curve was used to determine the optimal cut-off values for analyzing the risk. Results There were no significant differences in the overall survival (OS) between the REC ≥4.8% and <4.8% groups and the NER ≥13.7 and <13.7 groups before pembrolizumab (p=0.997 and 0.669, respectively). However, a significant difference in the OS was confirmed between the increased and decreased REC groups and between the decreased and increased NER groups at 3 weeks after pembrolizumab (p<0.001 and 0.002, respectively). Multivariate analyses revealed that an Eastern Cooperative Oncology Group Performance Status ≥2 (P=0.003), albumin <3.7 g/dl (p=0.002), LDH >246 U/L (p=0.011), disease site ≥3 organs (p=0.019), decreased posttreatment REC (3 weeks later) (p=0.002) and increased posttreatment NER (3 weeks later) (p=0.022) were independent prognostic factors for a worse OS. Conclusion An increased REC and decreased NER after pembrolizumab may be significant early predictive markers of improved clinical outcomes in patients with advanced UC receiving pembrolizumab.

show abstract

Section: Discussioncontrasting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

The Association of Clinical Outcomes with Posttreatment Changes in the Relative Eosinophil Counts and Neutrophil-to-Eosinophil Ratio in Patients with Advanced Urothelial Carcinoma Treated with Pembrolizumab

Furubayashi

Minato

Negishi

et al. 2021

CMAR

View full text Add to dashboard Cite

show abstract

“…We evaluated the tumor response according to Response Evaluation Criteria in Solid Tumors, version 1.1. 18 As reported previously, 19 , 20 the peripheral REC was measured at the same time as complete blood count measurements: before treatment and at three weeks after the start of pembrolizumab treatment. The patients’ clinical information and follow-up data were obtained from their medical records.…”

Section: Methodsmentioning

confidence: 94%

Association Between Immune-Related Adverse Events and Efficacy and Changes in the Relative Eosinophil Count Among Patients with Advanced Urothelial Carcinoma Treated by Pembrolizumab

Furubayashi¹,

Minato²,

Negishi³

et al. 2022

CMAR

View full text Add to dashboard Cite

Background To evaluate the association between immune-related adverse events (irAEs) and the clinical outcomes and also between irAEs and the post-treatment changes in the relative eosinophil count (REC) in advanced urothelial carcinoma (UC) patients treated with pembrolizumab. Materials and Methods This retrospective study analyzed 105 advanced UC patients treated with pembrolizumab after disease progression on platinum-based chemotherapy between January 2018 and June 2021. The association between the occurrence of irAEs and the efficacy of pembrolizumab was investigated. The change in the REC from before the initiation of pembrolizumab therapy, to three weeks after treatment and the incidence of irAEs were determined. Results Overall irAEs were associated with a significantly higher objective response rate (ORR) (58.8% vs 25.4%, P<0.001), a longer progression-free survival (PFS) (25.1 months vs 3.1 months, P< 0.001) and overall survival (OS) (31.2 months vs 11.5 months, P< 0.001) compared to patients without irAEs; however, grade ≥3 irAEs were not associated with the ORR (36.4% vs 36.2%, P=0.989), PFS (9.5 vs 5.5 months, P=0.249), or OS (not reached vs 13.7 months, P=0.335). Compared to a decreased REC at 3 weeks after pembrolizumab, an increased relative REC at 3 weeks was not associated with the incidence of any-grade irAEs (32.3% vs 32.5%, P=0.984) or of grade ≥3 irAEs (10.8% vs 10.0%, P=0.900). Multivariate analyses revealed a female sex (P=0.005), Eastern Cooperative Oncology Group Performance Status ≥1 (P=0.024), albumin <3.7 g/dl (P<0.001), decreased REC (3 weeks later) (P<0.001), and the absence of irAEs of any grade (P=0.002) to be independently associated with a worse OS. Conclusion Patients with irAEs showed a significantly better survival compared to patients without irAEs in advanced UC treated with pembrolizumab. An increased posttreatment REC may be a marker predicting improved clinical outcomes and it had no significant relationship with the incidence of irAEs.

show abstract

“…Furthermore, there is growing evidence among pre-clinical studies suggesting that eosinophils are essential cells in the TME for the anti-tumor activity observed with IO [ 15 , 16 ]. Recent clinical studies also reported that a higher baseline eosinophil count was predictive of improved ICI responses in melanoma [ 17 , 18 ], urothelial cancer [ 19 ], and head and neck cancer [ 20 ]. Besides the predictive value of the baseline eosinophil count, the interval increase in eosinophil count after initiation of ICIs was also observed among responders in lung cancer [ 21 , 22 ], melanoma [ 23 ], and kidney cancer [ 24 ].…”

Section: Introductionmentioning

confidence: 99%

The Association between a Decrease in On-Treatment Neutrophil-to-Eosinophil Ratio (NER) at Week 6 after Ipilimumab Plus Nivolumab Initiation and Improved Clinical Outcomes in Metastatic Renal Cell Carcinoma

Chen

Tucker

Brown

et al. 2022

Cancers

View full text Add to dashboard Cite

A lower baseline neutrophil-to-eosinophil ratio (NER) has been associated with improved responses to immune checkpoint inhibitors (ICI)-treated metastatic renal cell carcinoma (mRCC). This study investigated the decrease in NER at week 6 after ipilimumab/nivolumab (ipi/nivo) initiation and treatment responses in mRCC. A retrospective study of ipi/nivo-treated mRCC at two US academic cancer centers was conducted. A landmark analysis at week 6 was performed to assess the association between the change in NER and clinical responses (progression-free survival (PFS)/overall survival (OS)). Week 6 NER was modeled as a continuous variable, after log transformation (Ln NER), and a categorical variable by percent change. There were 150 mRCC patients included: 78% had clear cell histology, and 78% were IMDC intermediate/poor risk. In multivariable regression analysis, every decrease of 1 unit of Ln NER at week 6 was associated with improved PFS (adjusted hazard ratio (AHR): 0.78, p-value:0.005) and OS (AHR: 0.67, p-value: 0.002). When NER was modeled by percent change, decreased NER > 50% was associated with improved PFS (AHR: 0.55, p-value: 0.03) and OS (AHR: 0.37, p-value: 0.02). The decrease in week 6 NER was associated with improved PFS/OS in ipi/nivo-treated mRCC. Prospective studies are warranted to validate NER change as a biomarker to predict ICI responses.

show abstract

Pretreatment Eosinophil Counts in Patients With Advanced or Metastatic Urothelial Carcinoma Treated With Anti-PD-1/PD-L1 Checkpoint Inhibitors

Cited by 10 publications

References 31 publications

The Association of Clinical Outcomes with Posttreatment Changes in the Relative Eosinophil Counts and Neutrophil-to-Eosinophil Ratio in Patients with Advanced Urothelial Carcinoma Treated with Pembrolizumab

The Association of Clinical Outcomes with Posttreatment Changes in the Relative Eosinophil Counts and Neutrophil-to-Eosinophil Ratio in Patients with Advanced Urothelial Carcinoma Treated with Pembrolizumab

Association Between Immune-Related Adverse Events and Efficacy and Changes in the Relative Eosinophil Count Among Patients with Advanced Urothelial Carcinoma Treated by Pembrolizumab

The Association between a Decrease in On-Treatment Neutrophil-to-Eosinophil Ratio (NER) at Week 6 after Ipilimumab Plus Nivolumab Initiation and Improved Clinical Outcomes in Metastatic Renal Cell Carcinoma

Contact Info

Product

Resources

About