Targeted Cancer Therapies With Pericardial Effusions Requiring Pericardiocentesis Focusing on Immune Checkpoint Inhibitors

Abstract Immune checkpoint inhibitors have advanced the treatment paradigm of various cancers, achieving remarkable survival benefits. However, a myriad of immune-related adverse events (irAE) has been recognized in almost every organ system, presumably because of persistent immune system activation. Rheumatic symptoms such as arthralgia or myalgia are very common. More specific irAE are increasingly being reported. The most frequent ones are inflammatory arthritis, polymyalgia-like syndromes, myositis and sicca manifestations. These rheumatic irAE can develop in ∼5–10% of patients treated with immune checkpoint inhibitors, although true incidence rates cannot be estimated given the lack of prospective cohort studies, and likely underreporting of rheumatic irAE in oncology trials. In this review, we will provide a summary of the epidemiologic data reported for these rheumatic irAE, until more robust prospective longitudinal studies become available to further define the true incidence rate of rheumatic irAE in patients receiving these novel cancer therapies.

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Issues in Combination Cancer Therapies With Immune Checkpoint Inhibitors

Oncology Times ◽

10.1097/01.cot.0000546174.29722.01 ◽

2018 ◽

Vol 40 (17) ◽

pp. 1

Author(s):

Peggy Eastman

Keyword(s):

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Cancer Therapies

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Advancing Progress in the Development of Combination Cancer Therapies with Immune Checkpoint Inhibitors

10.17226/25405 ◽

2019 ◽

Author(s):

◽

Keyword(s):

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Cancer Therapies

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New emerging targets in cancer immunotherapy: the role of neoantigens

ESMO Open ◽

10.1136/esmoopen-2020-000684 ◽

2020 ◽

Vol 4 (Suppl 3) ◽

pp. e000684 ◽

Cited By ~ 3

Author(s):

Leticia De Mattos-Arruda ◽

Juan Blanco-Heredia ◽

Carmen Aguilar-Gurrieri ◽

Jorge Carrillo ◽

Julià Blanco

Keyword(s):

T Cell ◽

Cancer Immunotherapy ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Adoptive T Cell Therapy ◽

Treatment Modalities ◽

Clinical Samples ◽

Cancer Therapies ◽

T Cell Therapy

The success of cancer therapies with immune checkpoint inhibitors is transforming the treatment of patients with cancer and fostering cancer research. Therapies that target immune checkpoint inhibitors have shown unprecedented rates of durable long-lasting responses in patients with various cancer types, but only in a fraction of patients. Thus, novel approaches are needed to make immunotherapy more precise and also less toxic. The advances of next-generation sequencing technologies have allowed fast detection of somatic mutations in genes present in the exome of an individual tumour. Targeting neoantigens, the mutated peptides expressed only by tumour cells, may enable antitumour T-cell responses and tumour destruction without causing harm to healthy tissues. Currently, neoantigens can be identified in tumour clinical samples by using genomic-based computational tools. The two main treatment modalities targeting neoantigens that have been investigated in clinical trials are personalised vaccines and tumour infiltrating lymphocytes-based adoptive T-cell therapy. In this mini review, we discuss the promises and challenges for using neoantigens as emergent targets to personalise and guide cancer immunotherapy in a broader set of cancers.

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Predictable clinical benefits without synergy in trials of combination therapies with immune checkpoint inhibitors

10.21203/rs.3.rs-253936/v1 ◽

2021 ◽

Author(s):

Adam (C.) Palmer ◽

Benjamin Izar ◽

Haeun Hwangbo ◽

Peter Sorger

Keyword(s):

Survival Data ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Single Agent ◽

Progression Free Survival ◽

Phase Iii ◽

Cancer Therapies ◽

Immune Priming ◽

Clinical Benefits

Abstract Hundreds of clinical trials are currently underway testing combinations of Immune Checkpoint Inhibitors (ICIs) with other cancer therapies in the hope that drug combinations will be more effective than monotherapy. Enhanced efficacy is proposed to result from drug additivity or synergy involving mechanisms such as immune priming. In this paper we re-analyze progression free survival data from thirteen recent Phase III trials of ICI combinations and find that observed benefits are fully and accurately accounted for by an increased chance that each patient will respond to a single-agent, consistent with the predictions of drug independence, with no requirement for additive or synergistic efficacy. Thus, the likely anti-tumor efficacy of new ICI combinations can be reliably predicted from monotherapy data (Pearson r=0.98, P < 5×10-9, n = 4173 patients and 8 types of cancer), although predicting adverse effects is not yet possible. Realizing the clinical potential of drug additivity or synergy is likely to require biomarkers that identify patients in whom multiple constituents of a drug combination are active.

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Mathematical modelling of autoimmune myocarditis and the effects of immune checkpoint inhibitors

10.1101/2021.09.03.458857 ◽

2021 ◽

Author(s):

Solveig A. van der Vegt ◽

Liudmila Polonchuk ◽

Ken Wang ◽

Sarah L. Waters ◽

Ruth E. Baker

Keyword(s):

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Predictive Modelling ◽

Cancer Therapies ◽

Autoimmune Myocarditis ◽

Treatment Regimens ◽

Disease Characteristics ◽

Bifurcation Structures

AbstractAutoimmune myocarditis is a rare, but frequently fatal, side effect of immune checkpoint inhibitors (ICIs), a class of cancer therapies. Despite extensive experimental work on the causes, development and progression of this disease, much still remains unknown about the importance of the different immunological pathways involved. We present a mathematical model of autoimmune myocarditis and the effects of ICIs on its development and progression to either resolution or chronic inflammation. From this, we gain a better understanding of the role of immune cells, cytokines and other components of the immune system in driving the cardiotoxicity of ICIs. We parameterise the model using existing data from the literature, and show that qualitative model behaviour is consistent with disease characteristics seen in patients in an ICI-free context. The bifurcation structures of the model show how the presence of ICIs increases the risk of developing autoimmune myocarditis. This predictive modelling approach is a first step towards determining treatment regimens that balance the benefits of treating cancer with the risk of developing autoimmune myocarditis.

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Impact of pericardial effusion for patients receiving immune checkpoint inhibitors.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e14121 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e14121-e14121

Author(s):

Abir Khan ◽

Henry Zhang ◽

Christopher Chen ◽

Jacob Morgan ◽

Abdulrazzak Zarifa ◽

...

Keyword(s):

Ejection Fraction ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Case Series ◽

Left Ventricular ◽

Left Ventricular Ejection ◽

Ventricular Ejection Fraction ◽

Pericardial Effusions

e14121 Background: Various immune-related adverse events (IRAE) have been reported with the use of immune checkpoint inhibitors (ICI). Although a rare event, the increasing incidence of ICI related myocarditis and its reported high mortality raises concern. Cardiovascular IRAE such as pericardial effusions (PE) have been documented in case reports and case series but their clinical significance is unclear. Methods: Retrospective chart review was performed on 1075 patients receiving ICI between 2015 and 2017 with baseline echocardiograms without pericardial effusions and follow up echocardiograms at MD Anderson Cancer Center. We collected baseline characteristics, laboratory findings, echocardiograms, and dates of ICI initiation, PE development, last follow up and death. Overall survival (time from first ICI therapy to death or last follow up) was calculated. Univariate Fine-Gray regression analyses were conducted to identify variables associated with PE to account for death as a competing risk event. A p-value of less than 0.05 indicated statistical significance. Results: After initiation of ICI, 78 patients (7.3%) developed PE of which 45 patients died (58%) compared to 347 deaths (35%) out of the 997 patients without PE. The median follow-up time was 445 days. Univariate Fine-Gray analyses predicting PE demonstrated lower body surface area, lowest nadir in left ventricular ejection fraction (LVEF), higher troponin levels, lower platelet counts, absence of ectopy and hyperlipidemia, and lack of avelumab in therapy as well as a history of heart failure with preserved or reduced ejection fraction, hematologic cancer, and peripheral artery stents were significantly associated with higher incidence of PE. Conclusions: While the development of PE is an IRAE or progression of cancer itself cannot be determined, this study indicates patients receiving ICI who developed PE had higher mortality. Those with greater troponin levels and substantial decline in LVEF were shown to have a greater propensity of developing PE, suggesting the possibility of an underlying myopericarditis. If PE develops during ICI therapy, providers should consider an expedited workup and treatment of ICI related myocarditis.

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The Effects of Physical Activity on Cancer Patients Undergoing Treatment with Immune Checkpoint Inhibitors: A Scoping Review

Cancers ◽

10.3390/cancers13246364 ◽

2021 ◽

Vol 13 (24) ◽

pp. 6364

Author(s):

Amy L. Shaver ◽

Swapnil Sharma ◽

Nikita Nikita ◽

Daniel S. Lefler ◽

Atrayee Basu-Mallick ◽

...

Keyword(s):

Physical Activity ◽

Scoping Review ◽

Immune Checkpoint ◽

Clinical Studies ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Human Study ◽

Cancer Therapies ◽

Cancer Related Fatigue ◽

Physical Activity Interventions

Background: Cancer therapies are associated with multiple adverse effects, including (but not limited to) cancer-related fatigue (CRF). Fatigue is one of the most common side effects of immune checkpoint inhibitors (ICIs), occurring in up to 25% of patients. Physical activity has been shown to help reduce CRF through modulating the immune system, and may synergistically aid in the anti-tumor effects of ICIs. This review describes the nature and scope of evidence for the effects associated with concurrent physical activity while undergoing ICI therapy. Method: Scoping review methodology was utilized to identify studies, extract data, and collate and summarize results. Results: In literature published from January 2010 through to August 2021, only one human study and three pre-clinical studies met inclusion criteria. Conclusion: Existing evidence supports that physical activity is associated with decreased treatment-related toxicities such as CRF. However, further investigation is warranted. The dearth of clinical studies illustrates the need for more research to address this question, to guide patients and their providers in the application of appropriate physical activity interventions in those patients undergoing ICI.

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