Sites of metastasis and association with clinical outcome (CO) in advanced stage cancer patients (pts) treated with immunotherapy (IO)

Bilen, Mehmet Asım; Shabto, Julie M.; Martini, Dylan J.; Liu, Y.; Collins, Hannah; Akce, Mehmet; Carthon, Bradley Curtis; Shaib, Walid Labib; Alese, Olatunji B.; Steuer, Conor E.; Wu, Christina; Lawson, David H.; Kudchadkar, Ragini R.; Master, Viraj A.; El‐Rayes, Bassel F.; Ramalingam, Suresh S.; Owonikoko, Taofeek K.; Harvey, R. Donald

doi:10.1093/annonc/mdy288.092

Cited by 2 publications

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“…In many solid and liquid tumors, checkpoint inhibitor immunotherapies (CPIs) can reinvigorate preexisting antitumor immunity to achieve durable response rates. However, for melanoma, lung, kidney, and several other malignancies where CPIs have shown efficacy, accumulating evidence suggests that the presence of liver metastasis reduces response rate and progression-free and overall survival (1)(2)(3)(4)(5)(6)(7). For patients who have disease progression despite CPIs, there are limited salvage options.…”

Section: Introductionmentioning

confidence: 99%

Regulatory T cell control of systemic immunity and immunotherapy response in liver metastasis

et al. 2020

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Patients with cancer with liver metastasis demonstrate significantly worse outcomes than those without liver metastasis when treated with anti–PD-1 immunotherapy. The mechanism of liver metastases–induced reduction in systemic antitumor immunity is unclear. Using a dual-tumor immunocompetent mouse model, we found that the immune response to tumor antigen presence within the liver led to the systemic suppression of antitumor immunity. The immune suppression was antigen specific and associated with the coordinated activation of regulatory T cells (Tregs) and modulation of intratumoral CD11b+ monocytes. The dysfunctional immune state could not be reversed by anti–PD-1 monotherapy unless Treg cells were depleted (anti–CTLA-4) or destabilized (EZH2 inhibitor). Thus, this study provides a mechanistic understanding and rationale for adding Treg and CD11b+ monocyte targeting agents in combination with anti–PD-1 to treat patients with cancer with liver metastasis.

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Section: Introductionmentioning

confidence: 99%

Regulatory T cell control of systemic immunity and immunotherapy response in liver metastasis

et al. 2020

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“…This is particularly true for the liver, which is a secondary lymphoid organ that synthesizes acute phase reactants, complement proteins, and chemokines and houses a significant population of lymphoid cells such as T lymphocytes . Unsurprisingly, liver metastases are a poor prognostic factor in patients treated with ICI . A recent study suggests that this may be because liver metastases decrease the ratio of CD8 + /Foxp3 + regulatory T cells and the number of activated PD‐1 + /CTLA‐4 + T cells, indicating that liver metastases may have a systemic influence on tumor immunity .…”

Section: Discussionmentioning

confidence: 99%

Novel Risk Scoring System for Patients with Metastatic Renal Cell Carcinoma Treated with Immune Checkpoint Inhibitors

et al. 2019

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Background The International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) criteria are the gold standard for risk‐stratifying patients with metastatic renal cell cancer (mRCC). We developed a novel risk scoring system for patients with mRCC treated with immune checkpoint inhibitors (ICIs). Methods We performed a retrospective analysis of 100 ICI‐treated patients with mRCC at Winship Cancer Institute from 2015 to 2018. Several baseline variables were collected, including markers of inflammation, body mass index (BMI), and sites of metastatic disease, and all were considered for inclusion in our risk scoring system. Upon variable selection in multivariable model, monocyte‐to‐lymphocyte ratio (MLR), BMI, and number and sites of metastases at baseline were used for risk score calculation. Patients were categorized using four‐level risk groups as good (risk score = 0), intermediate (risk score = 1), poor (risk score = 2), or very poor (risk score = 3–4). Cox's proportional hazard model and the Kaplan‐Meier method were implemented for survival outcomes. Results Most patients were male (66%) with clear cell renal cell carcinoma (72%). The majority (71%) received anti–programmed cell death protein‐1 monotherapy. Our risk scoring criteria had higher Uno's concordance statistics than IMDC in predicting overall survival (OS; 0.71 vs. 0.57) and progression‐free survival (0.61 vs. 0.58). Setting good risk (MLR <0.93, BMI ≥24, and D_Met = 0) as the reference, the OS hazard ratios were 29.5 (95% confidence interval [CI], 3.64–238.9), 6.58 (95% CI, 0.84–51.68), and 3.75 (95% CI, 0.49–28.57) for very poor, poor, and intermediate risk groups, respectively. Conclusion Risk scoring using MLR, BMI, and number and sites of metastases may be an effective way to predict survival in patients with mRCC receiving ICI. These results should be validated in a larger, prospective study. Implications for Practice A risk scoring system was created for patients with metastatic renal cell carcinoma treated with immune checkpoint inhibitors. The results of this study have significant implications for practicing oncologists in the community and academic setting. Importantly, these results identify readily available risk factors that can be used clinically to risk‐stratify patients with metastatic renal cell carcinoma who are treated with immune checkpoint inhibitors.

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Sites of metastasis and association with clinical outcome (CO) in advanced stage cancer patients (pts) treated with immunotherapy (IO)

Cited by 2 publications

References 0 publications

Regulatory T cell control of systemic immunity and immunotherapy response in liver metastasis

Regulatory T cell control of systemic immunity and immunotherapy response in liver metastasis

Novel Risk Scoring System for Patients with Metastatic Renal Cell Carcinoma Treated with Immune Checkpoint Inhibitors

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