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Although programmed death-ligand 1 is currently the best available biomarker for first-line therapy with pembrolizumab for patients with non-small cell lung cancer and is a required companion test approved by the US Food and Drug Administration, programmed death-ligand 1 testing is an option (as a complementary test) for patients treated with nivol...
Context in source publication
Context 1
... immunotherapy has transformed the care of both hematologic and solid malignancies. Since the proposal of immune checkpoint blockade in 1996 and the regulatory approval of the first immune checkpoint inhibitor ipilimumab (Yervoy TM , Bristol-Myers- Squibb) in 2011, five more immune checkpoint inhibi- tors (Table 1) have been approved by the US Food and Drug Administration (FDA) to date, representing a shift in treatment paradigm from cytotoxic chemother- apy to therapies that focus on the immune modulation of the tumor microenvironment. 1,2 Principle of anti-tumor T-cell immunity This change in paradigm is made possible by a number of key scientific breakthroughs: (1) researchers in the 1980s demonstrated that full T-cell activation required not only the binding of T-cell receptor (TCR) to the peptide antigen/major histocompatibility complex (MHC), but also co-stimulatory signals by accessory cells (such as antigen presenting cells, e.g. ...
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Background:
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Materia...
Citations
... It is wellknown that e.g. PD-L1 as a predictive biomarker has significant shortcommings in its analytical and clinical validity [61,62], but it is still part of clinical practice and guidelines [63]. Seemingly technical decisions on tissue fixation, assay properties and thresholds for positive tests also raise important normative challenges [17]. ...
Background
In precision medicine biomarkers stratify patients into groups that are offered different treatments, but this may conflict with the principle of equal treatment. While some patient characteristics are seen as relevant for unequal treatment and others not, it is known that they all may influence treatment decisions. How biomarkers influence these decisions is not known, nor is their ethical relevance well discussed.
Methods
We distributed an email survey designed to elicit treatment preferences from Norwegian doctors working with cancer patients. In a forced-choice conjoint analysis pairs of hypothetical patients were presented, and we calculated the average marginal component effect of seven individual patient characteristics, to estimate how each of them influence doctors’ priority-setting decisions.
Results
A positive biomarker status increased the probability of being allocated the new drug, while older age, severe comorbidity and reduced physical function reduced the probability. Importantly, sex, education level and smoking status had no significant influence on the decision.
Conclusion
Biomarker status is perceived as relevant for priority setting decisions, alongside more well-known patient characteristics like age, physical function and comorbidity. Based on our results, we discuss a framework that can help clarify whether biomarker status should be seen as an ethically acceptable factor for providing unequal treatment to patients with the same disease.
... To the best of our knowledge, this is the first real-world study investigating the potential interactions between influenza vaccines and ICIs resulting in myocarditis or pericarditis in cancer patients, by assessing spontaneous reports submitted to the VAERS and VigiBase ® . This global post-marketing safety study stems from recent conflicting realworld evidence surrounding the possible exacerbation of irAEs with influenza vaccines in patients treated with ICIs [14,15,[24][25][26][27][28][29], thus joining in the wider debate on the bidirectional relationship between immunotherapy and the influenza vaccination, potentially affecting the clinical and humoral efficacy of the vaccine, performance of ICIs, and safety [14]. ...
Background:
Evidence on whether the influenza vaccine could exacerbate immune-related adverse events, including myopericarditis (MP), in patients treated with immune checkpoint inhibitors (ICIs), is still conflicting. We explored this issue through a global real-world approach.
Methods:
We queried the Vaccine Adverse Event Reporting System (VAERS) and VigiBase to retrieve cases of MP in which the influenza vaccine and ICIs were recorded as suspect and were concomitantly reported. For the included cases, causality assessment and Drug Interaction Probability Scale (DIPS) algorithms were applied.
Results:
There were 191 and 399 reports of MP with the influenza vaccine that were retrieved (VAERS and VigiBase, respectively). No case of MP reporting the concomitant use of ICIs and the influenza vaccine was found in VAERS, while three cases of myocarditis were retrieved in VigiBase. All of the cases were unclassifiable for a causality assessment because of the lack of data concerning latency. According to the DIPS, one report was categorized as possible and two as doubtful.
Conclusion:
The paucity of cases coupled with the doubtful causality assessment make the potential interaction between influenza vaccines and ICIs in cancer patients negligible from clinical and epidemiological standpoints. These findings support the cardiovascular safety of the influenza vaccination, which remains strongly recommended in cancer patients, especially in the current COVID-19 era.
... Zudem wird die Impfung mit dem Influenzatotimpfstoff unter der Therapie mit anti-PD-1-AK bzw. anti-PD-L1-AK befürwortet [ExpertInnenkonsens]. Zur Influenzaimpfung unter der Therapie mit dem anti-CTLA-4-AK Ipilimumab existieren nur Einzelfallberichte, die eine Pause von 6-8 Wochen nach der letzten Gabe empfehlen [56]. Sofern Autoimmunreaktionen nach Impfung auftreten, sollten diese gemäß den Empfehlungen zur Behandlung von Autoimmunreaktionen bei CI-Gabe eingeordnet und behandelt werden (siehe auch: Clinical Practice Guide line der American Society of Clinical Oncology unter https://ascopubs.org/ ...
... As the use of immunotherapy for treating various types of cancer becomes more widespread, several issues require investigation to determine their possible impact on the outcome of cancer patients treated with anti-PD-1/PD-L1 immune checkpoint inhibitors (CKIs) (1). Thus, the respective effects of concomitant medications, concurrent treatments and other possible immunomodulatory events in the clinical history of patients prior to the initiation of immunotherapy, or during its course, have been largely explored in the recent years, obtaining a wide range of controversial evidence (1)(2)(3)(4)(5). ...
... As the use of immunotherapy for treating various types of cancer becomes more widespread, several issues require investigation to determine their possible impact on the outcome of cancer patients treated with anti-PD-1/PD-L1 immune checkpoint inhibitors (CKIs) (1). Thus, the respective effects of concomitant medications, concurrent treatments and other possible immunomodulatory events in the clinical history of patients prior to the initiation of immunotherapy, or during its course, have been largely explored in the recent years, obtaining a wide range of controversial evidence (1)(2)(3)(4)(5). For example, it seems that the use of corticosteroids or antibiotics before or with CKIs may decrease efficacy of the latter, whereas the use of influenza vaccine may be beneficial irrespective of its anti-infectious efficacy (2)(3)(4). ...
In the present study, the influence of purely palliative radiotherapy (pRT) on the outcomes of patients with advanced cancer undergoing immune checkpoint blockade was evaluated. Patients were stratified into three groups: Patients who had received pRT within 6 months prior to the initiation of immunotherapy (previous pRT); patients who received pRT during immunotherapy (concurrent pRT); and patients who did not receive RT prior to or during immu-notherapy (no RT group), and these groups were compared. The median overall survival (mOS), median progression free survival (mPFS) and median time-to-treatment failure (mTTF) for the previous pRT group were significantly shorter compared with the no RT group (mOS, 3.6 vs. 12.1 months, respectively, P=0.0095; mPFS 1.8 vs. 5.4 months, respectively, P=0.0016; mTTF 1.8 vs. 5.7 months, respectively, P=0.0035). The concurrent pRT group had a longer mTTF compared with the previous pRT group and similar outcomes to the no RT group. In the previous pRT group, 26.9% of the patients experienced immune-related adverse events compared with 40.1% of patients in the no RT group. Despite the use of pRT during immunotherapy being considered safe, the results of the present study suggest that pRT has a negative effect on immune balance.
... In the current study, we designed dual pH/reduction-sensitive nanoparticles with a poly-L-lysine-lipoic acid (PLL-LA) reductionresponsive core and modified with a tumor extracellular pH (pHe)triggered shedding PEG layer (sPEG) for the efficient codelivery of DOX and PD-L1 siRNA (siPD-L1). B16 cells (malignant melanoma cell lines) were chosen as model, and showed extremely high mortality and high expression of PD-L1 protein on the surface (Chung, 2018). ...
Cancer cells have been reported to exhibit high resistance against immune system recognition through various cell intrinsic and extrinsic mechanisms. Considerable challenges have been encountered in monotherapy with chemotherapeutics to attain the desired antitumor efficacy. In this study, a nanodelivery system was designed to incorporate doxorubicin (DOX) and programmed death‐ligand 1 (PD‐L1) small interfering RNA (siRNA), that is, siPD‐L1. DOX and siPD‐L1 were formed from a stimuli‐responsive polymer with a poly‐L‐lysine–lipoic acid reduction‐sensitive core and a tumor extracellular pH‐stimulated shedding polyethylene glycol layer. The codelivery system was stable under physiological pH conditions and demonstrated enhanced cellular uptake at the tumor site. Moreover, the combined treatment of DOX and siPD‐L1 exhibited improved antitumor effect in vitro and in vivo compared with either modality alone. The combination of chemotherapy and immunotherapy presented in this work through the codelivery of a chemotherapeutic agent and a gene‐silencing agent (siRNA) may provide a new strategy for cancer treatment.
... The current advent of the new immunotherapy with immune checkpoint inhibitors (CKI), recently approved with multiple indications for advanced cancer patients (Bersanelli and Buti, 2017;Banna et al., 2018), overturned all our certainties about traditionally "simple" issues, such as the concomitant administration of common medications: antibiotics, corticosteroids, and even vaccines (Derosa et al., 2018;Garant et al., 2017;Chung, 2018). On the other hand, the influenzarelated morbidity and mortality of cancer patients treated with anti-PD-1/PD-L1 CKIs have not been explored yet. ...
Influenza vaccination is recommended for advanced cancer patients, since impaired immunity is presumed to be due not only to the tumor itself but also to immunosuppressive treatments, such as chemotherapy and radiotherapy. The recent advances in the systemic management of metastatic solid tumors, with the introduction of immune checkpoint inhibitors for several indications in clinical practice, has re-actualized simple clinical issues, such as the vaccinal recommendations and counseling, for which common sense is not enough to support pragmatic choices. In the present review, we summarized the evidence about influenza vaccine administration during immune checkpoint blockade, emphasizing the need of prospective data to definitely guide our advices to a growing group of cancer patients.
... At this time, PD-L1 testing is the best predictor of clinical response, particularly for pembrolizumab, where it is required for use as single-agent therapy. PD-L1 testing is sometimes also used with other checkpoint inhibitors as an FDA-approved nonessential complementary test, although that is not required for treatment (Chung, 2018;Kazandjian et al., 2016). The Society for Immunotherapy of Cancer (SITC) consensus statement on immunotherapy for NSCLC indicates that the analysis of PD-L1 expression should be routine for all patients with newly diagnosed advanced NSCLC (Brahmer et al., 2018a). ...
Programmed cell death protein 1 receptor and programmed cell death ligand 1 (PD-L1) inhibitors are immune checkpoint inhibitors (ICIs) that provide a survival benefit for select patients with advanced non-small cell lung cancer (NSCLC). Nivolumab, pembrolizumab, and atezolizumab are second-line therapies for advanced NSCLC after chemotherapy failure. Pembrolizumab and atezolizumab are also approved as first-line treatment for advanced NSCLC, and durvalumab is a PD-L1 inhibitor indicated as consolidation therapy in individuals with locally advanced NSCLC. The novel mechanism of action of these agents provides clear efficacy benefits to many NSCLC patients without good alternatives, but it may also result in unique immune-related adverse events that many health-care providers are unfamiliar with or uncertain about how to diagnosis and manage. Highlighting the resources of the Immuno-Oncology Essentials Initiative, particularly the Care Step Pathways (CSPs), this article addresses the role of the advanced practice provider in administration, side-effect identification and management, and education of patients with advanced NSCLC receiving ICI therapy. The diagnosis and management of pneumonitis, hypophysitis, diabetes mellitus, and arthralgias/myalgias are examined in detail, addressing special considerations in the NSCLC population.
The use of immune checkpoint inhibitors (ICIs) in cancer patients is rapidly growing. However, the potential impact of some widely used concomitant medications is still largely unclear. Emerging data suggest that gut microbiota may affect the efficacy of ICIs, leading to the hypothesis that concurrent antibiotics and proton pump inhibitors use could have a detrimental effect. In addition, steroid use might potentially impair the activity of immunotherapy, due its known immunosuppressive effects, and some safety concerns have been raised in patients receiving commonly used vaccination during ICIs. However, all randomized trials evaluating ICIs consistently excluded patients receiving high corticosteroid doses and data regarding other concomitant medications are lacking. Recently, several retrospective studies have tried to address this unmet medical need. Herein we discuss the latest evidence on the influence of these medications, critically analyzing the data reported so far and the possible implications in our clinical practice.
