scholarly journals Treatment with therapeutic anticoagulation is not associated with immunotherapy response in advanced cancer patients

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Paul Johannet ◽  
Amelia Sawyers ◽  
Nicholas Gulati ◽  
Douglas Donnelly ◽  
Samuel Kozloff ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Advanced Cancer ◽  
Immune Checkpoint ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Progression Free Survival ◽  
Immune Checkpoint Blockade ◽  
Coagulation Cascade ◽  
Advanced Cancer Patients ◽  
Clinical Endpoints

Abstract Background Recent preclinical data suggest that there may be therapeutic synergy between immune checkpoint blockade and inhibition of the coagulation cascade. Here, we investigate whether patients who received immune checkpoint inhibitors (ICI) and were on concomitant anticoagulation (AC) experienced better treatment outcomes than individuals not on AC.Affiliation: Kindly confirm if corresponding authors affiliation is identified correctly.The corresponding author's affiliation is correct. Methods We studied a cohort of 728 advanced cancer patients who received 948 lines of ICI at NYU (2010–2020). Patients were classified based on whether they did (n = 120) or did not (n = 828) receive therapeutic AC at any point during their treatment with ICI. We investigated the relationship between AC status and multiple clinical endpoints including best overall response (BOR), objective response rate (ORR), disease control rate (DCR), progression free survival (PFS), overall survival (OS), and the incidence of bleeding complications.Affiliations: Journal instruction requires a country for affiliations; however, this is missing in affiliations 1 to 5. Please verify if the provided country is correct and amend if necessary.The country is correct for all affiliations (1 - 5). Results Treatment with AC was not associated with significantly different BOR (P = 0.80), ORR (P =0.60), DCR (P =0.77), PFS (P = 0.59), or OS (P =0.64). Patients who received AC were significantly more likely to suffer a major or clinically relevant minor bleed (P = 0.05). Conclusion AC does not appear to impact the activity or efficacy of ICI in advanced cancer patients. On the basis of our findings, we caution that there is insufficient evidence to support prospectively evaluating the combination of AC and immunotherapy.

scholarly journals The Risks and Benefits of Immune Checkpoint Blockade in Anti-AChR Antibody-Seropositive Non-Small Cell Lung Cancer Patients

Cancers ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 140 ◽  
Author(s):  
Koichi Saruwatari ◽  
Ryo Sato ◽  
Shunya Nakane ◽  
Shinya Sakata ◽  
Koutaro Takamatsu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Patients ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Antibody Therapy ◽  
Lung Squamous Cell Carcinoma ◽  
Complete Response ◽  
Immune Checkpoint Blockade ◽  
Advanced Cancer Patients

Background: Anti-programmed cell death 1 (PD-1) monoclonal antibodies (Abs) unleash an immune response to cancer. However, a disruption of the immune checkpoint function by blocking PD-1/PD-ligand 1(PD-L1) signaling may trigger myasthenia gravis (MG) as a life-threatening immune-related adverse event. MG is a neuromuscular disease and is closely associated with being positive for anti-acetylcholine receptor (anti-AChR) Abs, which are high specific and diagnostic Abs for MG. Methods: A 72-year-old man was diagnosed with chemotherapy-refractory lung squamous cell carcinoma and nivolumab was selected as the third-line regimen. We describe the first report of an anti-AChR Ab-seropositive lung cancer patient achieving a durable complete response (CR) to an anti-PD-1 antibody therapy. To further explore this case, we performed multiplex immunofluorescence analysis on a pretreatment tumor. Results: The patient achieved a durable CR without developing MG. However, the levels of anti-AChR Abs were elevated during two years of anti-PD-1 antibody therapy. The tumor of the subclinical MG patient had high PD-L1 expression and an infiltrated–inflamed tumor immune microenvironment. Conclusions: This study suggests that immune checkpoint inhibitors can be safely used and provide the benefits for advanced cancer patients with immunologically ‘hot’ tumor even if anti-AChR Abs are positive. Although careful monitoring clinical manifestation in consultation with neurologist is needed, immune checkpoint inhibitors should be considered as a treatment option for asymptomatic anti-AChR Ab-seropositive cancer patients.

Early changes in lymphocyte/monocyte ratio on-treatment as a prognostic marker to predict overall survival in patients with advanced cancer treated with immune checkpoint inhibitors

2021 ◽  
Author(s):  
Sandip H. Patel ◽  
Songzhu Zhao ◽  
Mingjia Li ◽  
Lai Wei ◽  
Marium Husain ◽  
...  
Keyword(s):  
Overall Survival ◽  
Cancer Patients ◽  
Advanced Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Predictive Biomarker ◽  
Advanced Cancer Patients ◽  
High Baseline

Abstract Background A low absolute lymphocyte/monocyte ratio (LMR) in the peripheral blood is associated with poor prognosis in various cancers; however, its role as a predictive biomarker has not been well defined in the era of treatment with immune checkpoint inhibitors (ICI). Methods We queried a database of advanced cancer patients treated with at least one dose of ICI from 2011 to 2017 to study the association of LMR with overall survival (OS). We calculated LMR at baseline and a median of 21 days after the first cycle of ICI (on-treatment LMR), and defined low if < 2 and high if ≥ 2. OS was calculated from the initiation of ICI to date of death or censored at last follow-up. Results 1077 patients met the criteria for this study. Patients with low baseline LMR had a shorter median OS compared to patients with a high baseline LMR (8.5 vs 18.1 months, p < 0.01). In patients with a low baseline LMR, who on-treatment LMR increased to high had longer median OS compared to those whose on-treatment LMR remained low (16.8 vs 7.8 months, p < 0.001). Patients with a high baseline LMR and in whom on-treatment LMR remained high had longer median OS compared to patients with low on-treatment LMR (23.9 vs 9.2 months, p < 0.001). In multivariate analysis, high on-treatment LMR was most strongly associated with longer survival compared to low on-treatment LMR, regardless of baseline LMR. Conclusions Higher baseline and early changes in on-treatment LMR are associated with improved OS in cancer patients receiving ICI.

scholarly journals Symptomatic COVID-19 in advanced-cancer patients treated with immune-checkpoint inhibitors: prospective analysis from a multicentre observational trial by FICOG

2020 ◽  
Vol 12 ◽  
pp. 175883592096846
Author(s):  
Melissa Bersanelli ◽  
Diana Giannarelli ◽  
Ugo De Giorgi ◽  
Sandro Pignata ◽  
Massimo Di Maio ◽  
...  
Keyword(s):  
Mortality Rate ◽  
Influenza Vaccination ◽  
Cancer Patients ◽  
Advanced Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Advanced Cancer Patients ◽  
Laboratory Confirmation ◽  
The Difference

Background: This prospective, multicentre, observational INVIDIa-2 study is investigating the clinical efficacy of influenza vaccination in advanced-cancer patients receiving immune-checkpoint inhibitors (ICIs), enrolled in 82 Italian centres, from October 2019 to January 2020. The primary endpoint was the incidence of influenza-like illness (ILI) until 30 April 2020. All the ILI episodes, laboratory tests, complications, hospitalizations and pneumonitis were recorded. Therefore, the study prospectively recorded all the COVID-19 ILI events. Patients and methods: Patients were included in this non-prespecified COVID-19 analysis, if alive on 31 January 2020, when the Italian government declared the national emergency. The prevalence of confirmed COVID-19 cases was detected as ILI episode with laboratory confirmation of SARS-CoV-2. Cases with clinical-radiological diagnosis of COVID-19 (COVID-like ILIs), were also reported. Results: Out of 1257 enrolled patients, 955 matched the inclusion criteria for this unplanned analysis. From 31 January to 30 April 2020, 66 patients had ILI: 9 of 955 cases were confirmed COVID-19 ILIs, with prevalence of 0.9% [95% confidence interval (CI): 0.3–2.4], a hospitalization rate of 100% and a mortality rate of 77.8%. Including 5 COVID-like ILIs, the overall COVID-19 prevalence was 1.5% (95% CI: 0.5–3.1), with 100% hospitalization and 64% mortality. The presence of elderly, males and comorbidities was significantly higher among patients vaccinated against influenza versus unvaccinated ( p = 0.009, p < 0.0001, p < 0.0001). Overall COVID-19 prevalence was 1.2% for vaccinated (six of 482 cases, all confirmed) and 1.7% for unvaccinated (8 of 473, 3 confirmed COVID-19 and 5 COVID-like), p = 0.52. The difference remained non-significant, considering confirmed COVID-19 only ( p = 0.33). Conclusion: COVID-19 has a meaningful clinical impact on the cancer-patient population receiving ICIs, with high prevalence, hospitalization and an alarming mortality rate among symptomatic cases. Influenza vaccination does not protect from SARS-CoV-2 infection.

scholarly journals Results from a Meta-analysis of Combination of PD-1/PD-L1 and CTLA-4 Inhibitors in Malignant Cancer Patients: Does PD-L1 Matter?

2021 ◽  
Vol 12 ◽  
Author(s):  
Yuqian Feng ◽  
Huimin Jin ◽  
Kaibo Guo ◽  
Yuying Xiang ◽  
Yiting Zhang ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Cancer Patients ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Malignant Tumors ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Objective Response ◽  
Progression Free Survival ◽  
Combination Immunotherapy

Background: Combination therapy with immune checkpoint inhibitors (ICIs) has been widely used for clinical treatment in recent years, which has a better survival benefit. However, not all patients can derive clinical benefit from combination immunotherapy. Therefore, it is necessary to explore the biomarkers of combination immunotherapy.Methods: We retrieved articles from electronic databases including PubMed, EMBASE and Cochrane. The statistical analysis was performed using RevMan software. Progression free survival (PFS), overall survival (OS) and objective response rate (ORR) were the outcome indicators. In the unselect population, we compared combination therapy with other treatments. In addition, we also conducted subgroup analysis on PFS, OS and ORR according to PD-L1 status.Results: Seven studies were included in the analysis for a total of 3,515 cases. In the unselected population, we found that combination therapy has longer PFS, OS, and better ORR than other treatments for cancer patients. The longer PFS was showed in PD-L1 ≥ 5% cases (HR = 0.64, 95% CI: 0.56–0.76; p &lt; 0.001) than PD-L1 ≥ 1% cases (HR = 0.72, 95% CI: 0.66–0.79; p &lt; 0.001), while ORR and OS have not related to the status of PD-L1.Conclusion: This study supported the efficacy of combination therapy with immune checkpoint inhibitors (ICIs), and also showed that PFS in patients with malignant tumors is positively correlated with PD-L1 expression. Due to the limited number of trials included, more high-quality clinical randomized controlled trials should be conducted to confirm the review findings.

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