Dataset Information

Immune-related adverse events and prognosis in patients with upper gastrointestinal cancer treated with nivolumab.

ABSTRACT:

Background

Immune checkpoint inhibitors (ICIs) are increasingly being used for the treatment of upper gastrointestinal cancers [esophageal cancer and gastric cancer (GC)]. They cause imbalances in immunological tolerance, resulting in immune-related adverse events (irAEs). Although irAEs have been reported to be associated with the efficacy of ICIs in some cancers, the relationship between irAEs and prognosis of upper gastrointestinal cancers remains unknown. This study aimed to investigate the prognostic impact of irAEs in patients with advanced or recurrent upper gastrointestinal cancer treated with nivolumab.

Methods

We retrospectively divided the patients (n=96) who received nivolumab into two groups: the irAEs group (n=41) and non-irAEs group (n=55), according to the Common Terminology Criteria for Adverse Events ver. 5.0.

Results

irAEs were significantly associated with good performance status and high serum albumin levels (all P<0.05). The irAEs group had a significantly longer overall survival (OS) than the non-irAEs group [log-rank P=0.003; univariate hazard ratio (HR) =0.36, 95% confidence interval (CI) =0.21-0.65, P<0.01; multivariate HR =0.47, 95% CI =0.26-0.88, P=0.018]. Importantly, in both esophageal cancer and GC, the irAEs group experienced favorable clinical outcomes compared with the non-irAEs group. In the multivariate analysis, male sex (P<0.01), presence of irAEs (P=0.018), and good pretreatment performance status (P<0.01) were independent prognostic factors.

Conclusions

Among patients with upper gastrointestinal cancer treated with nivolumab, the prognosis of patients who developed irAEs was better than that of patients who did not develop irAEs. Long-term continuation of nivolumab by early detection of irAEs and an appropriate response to irAEs are important.

SUBMITTER: Hara Y

PROVIDER: S-EPMC9830324 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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Publications

Immune-related adverse events and prognosis in patients with upper gastrointestinal cancer treated with nivolumab.

Hara Yoshihiro Y Baba Yoshifumi Y Toihata Tasuku T Harada Kazuto K Ogawa Katsuhiro K Iwatsuki Masaaki M Iwagami Shiro S Miyamoto Yuji Y Yoshida Naoya N Baba Hideo H

Journal of gastrointestinal oncology 20221201 6

<h4>Background</h4>Immune checkpoint inhibitors (ICIs) are increasingly being used for the treatment of upper gastrointestinal cancers [esophageal cancer and gastric cancer (GC)]. They cause imbalances in immunological tolerance, resulting in immune-related adverse events (irAEs). Although irAEs have been reported to be associated with the efficacy of ICIs in some cancers, the relationship between irAEs and prognosis of upper gastrointestinal cancers remains unknown. This study aimed to investig ...[more]

PMID: 36636073

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Project description:BackgroundTreatment with ipilimumab, a fully human anti-CTLA-4 antibody approved for the treatment of advanced melanoma, is associated with some immune-related adverse events (irAEs) such as colitis (gastrointestinal irAE, or GI irAE) and skin rash, which are managed by treatment guidelines. Nevertheless, predictive biomarkers that can help identify patients more likely to develop these irAEs could enhance the management of these toxicities.MethodsTo identify candidate predictive biomarkers associated with GI irAEs, gene expression profiling was performed on whole blood samples from 162 advanced melanoma patients at baseline, 3 and 11 weeks after the start of ipilimumab treatment in two phase II clinical trials (CA184004 and CA184007). Overall, 49 patients developed Grade 2 or higher (grade 2+) GI irAEs during the course of treatment. A repeated measures analysis of variance (ANOVA) was used to evaluate the differences in mean expression levels between the GI irAE and No-GI irAE groups of patients at the three time points.ResultsIn baseline samples, 27 probe sets showed differential mean expression (≥ 1.5 fold, P ≤ 0.05) between the GI irAE and No-GI irAE groups. Most of these probe sets belonged to three functional categories: immune system, cell cycle, and intracellular trafficking. Changes in gene expression over time were also characterized. In the GI irAE group, 58 and 247 probe sets had a ≥ 1.5 fold change in expression from baseline to 3 and 11 weeks after first ipilimumab dose, respectively. In particular, on-treatment expression increases of CD177 and CEACAM1, two neutrophil-activation markers, were closely associated with GI irAEs, suggesting a possible role of neutrophils in ipilimumab-associated GI irAEs. In addition, the expression of several immunoglobulin genes increased over time, with greater increases in patients with grade 2+ GI irAEs.ConclusionsGene expression profiling of peripheral blood, sampled before or early in the course of treatment with ipilimumab, resulted in the identification of a set of potential biomarkers that were associated with occurrence of GI irAEs. However, because of the low sensitivity of these biomarkers, they cannot be used alone to predict which patients will develop GI irAEs. Further investigation of these biomarkers in a larger patient cohort is warranted.

Project description:BackgroundOverweight and obese patients with solid tumors receiving anti-programmed cell death-1 (PD-1)/PD-ligand-1(PD-L1) immune checkpoint inhibitors exhibit improved survival and higher risk of immune-related adverse events (irAEs) than those with a normal body mass index (BMI). In classic Hodgkin lymphoma (cHL), the impact of BMI on survival and immune-related toxicity is unknown. We evaluated for the first time associations of BMI with survival and irAEs in patients with relapsed/refractory (RR)-cHL undergoing PD-1 blockade.MethodsData from a multicenter study on 133 patients treated with the anti-PD1 antibody nivolumab (July 2015-December 2016) were retrieved from a prospective database. Progression-free (PFS), overall survival (OS), incidence and severity of irAEs according to BMI categories were estimated by Kaplan-Meier method, landmark-analyses and Cox regressions.ResultsPatients, mostly males (63%, n = 84) with a median age of 35 years (range, 15-82), advanced stage (75%), B symptoms (63%), bulky disease (24%), a median of 4 previous treatments (range, 1-9), received a median of 18 nivolumab doses (range, 1-57). No statistically significant differences across BMI subgroups emerged as to PFS, with 1-year rates of 67.1% for both normal weight (n = 66; 49.6%) and overweight (n = 31; 23.3%) patients. Underweight (n = 12; 9%) and obese (n = 24; 18%) patients had a 1-year PFS of 54.5% and 49%, respectively. In survival analyses, BMI either as a continuous (P = 0.5) or categorical (P for trend = 0.63) variable failed to associate with PFS. Response rates and time-to-response did not cluster in any BMI subset. No BMI-related differences in OS emerged across normal, overweight and obese patients but underweight patients had the worst survival. Occurrence of irAEs of whatever severity did not statistically associate with BMI.ConclusionsIn patients with RR-cHL receiving nivolumab, no statistically significant differences emerged in response rates, PFS and OS across BMI categories of normal weight, overweight and obese. Overweight/obese patients did not display an increased risk of irAEs. The exquisite sensitivity to anti-PD-1 antibodies, the unique cytokine milieu and effector pathways triggered by nivolumab in cHL, may represent biologic 'equalizers' counteracting the immunoregulatory effects of adiposity. Differently from solid tumors, BMI is not associated with treatment efficacy and immune-related toxicity and does not represent a predictive tool for PD-1-targeted immunotherapies in cHL.

Dataset Information

Immune-related adverse events and prognosis in patients with upper gastrointestinal cancer treated with nivolumab.

Background

Methods

Results

Conclusions

Publications

Immune-related adverse events and prognosis in patients with upper gastrointestinal cancer treated with nivolumab.

Similar Datasets

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