Unleashing the power of immunotherapy and targeted therapy combinations: Advancing cancer care or discovering unknown toxicities?

2021 ◽  
pp. 107815522098423
Author(s):  
Daniel J Przybylski ◽  
Jason J Bergsbaken ◽  
Jennifer K Piccolo
Keyword(s):  
Patient Outcomes ◽  
Immune Checkpoint Inhibitor ◽  
Kinase Inhibitor ◽  
Checkpoint Inhibitor ◽  
Dual Therapy ◽  
Careful Consideration ◽  
Future Research ◽  
The Past ◽  
Tumor Types ◽  
Improve Patient

Objective The purpose of this review was to summarize the triumphs and pitfalls of tyrosine kinase inhibitor (TKI) and immune checkpoint inhibitor (ICI) combinations. Data sources: A literature review of PubMed was conducted and studies were included if they were classified as a clinical trial and assessed TKI and ICI combinations for solid tumor malignancies. Dates of literature search included January 1, 1988 through September 22, 2019. Data summary: In the past decade, TKI and ICI monotherapy strategies have changed the management of many advanced solid tumors through their unique mechanisms of action. Preclinical data suggests that TKIs may be able to sensitize tumors to ICI therapy via direct and indirect pathways; however, optimal mechanisms to support various TKI and ICI combinations have yet to be determined. The FDA recently approved TKI and ICI combinations for renal cell carcinoma, endometrial carcinoma, and melanoma. Several other tumor types currently have TKI and immunotherapy combinations under investigation with mixed results. Dual therapy with TKIs and immunotherapy have the potential to be synergistic and improve patient outcomes; however, careful consideration will need to be taken in regard to what TKI and immunotherapy are combined. Conclusions Future research will be needed to determine appropriate sequencing of TKIs and ICIs after progression on combination therapy. Continued research is necessary to determine optimal dual TKI and immunotherapy options.

CMV coinfection in treatment refractory immune checkpoint inhibitor colitis

2020 ◽  
Vol 13 (5) ◽  
pp. e233519
Author(s):  
Kevin B Harris ◽  
Pauline Funchain ◽  
Brian B Baggott
Keyword(s):  
Case Report ◽  
Patient Outcomes ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Treatment Refractory ◽  
Cmv Colitis ◽  
Improve Patient

As immune checkpoint inhibitors (ICIs) are increasingly used, clinicians are more frequently encountering the side effects of these therapies. ICIs have been implicated in numerous adverse effects against healthy tissues. We present a case of a patient who developed treatment refractory checkpoint inhibitor colitis. Following colonoscopy, it was discovered that this patient had cytomegalovirus (CMV) coinfection. This case report highlights the importance of undertaking an appropriate assessment, including endoscopic and histologic investigation, of patients with presumed ICI colitis. Accurately diagnosing a superimposed CMV colitis changes clinical management and can improve patient outcomes.

scholarly journals Bacteria and Sepsis: Microbiome to the Rescue?

2021 ◽  
Vol 10 (16) ◽  
pp. 3578
Author(s):  
Hansol Kang ◽  
Ryan M. Thomas
Keyword(s):  
Clinical Trials ◽  
Septic Patient ◽  
Patient Outcomes ◽  
Host Response ◽  
Patient Survival ◽  
Future Research ◽  
Confounding Factors ◽  
The Past ◽  
Sepsis Survival ◽  
Improve Patient

The microbiome is the metagenome of all microbes that live on and within every individual, and evidence for its role in the pathogenesis of a variety of diseases has been increasing over the past several decades. While there are various causes of sepsis, defined as the abnormal host response to infection, the host microbiome may provide a unifying explanation for discrepancies that are seen in septic patient survival based on age, sex, and other confounding factors. As has been the case for other human diseases, evidence exists for the microbiome to control patient outcomes after sepsis. In this review, associative data for the microbiome and sepsis survival are presented with causative mechanisms that may be at play. Finally, clinical trials to manipulate the microbiome in order to improve patient outcomes after sepsis are presented as well as areas of potential future research in order to aid in the clinical treatment of these patients.

scholarly journals Paraneoplastic neurological syndromes: clinical presentations and management

2021 ◽  
Vol 14 ◽  
pp. 175628642098532
Author(s):  
Michelle F. Devine ◽  
Naga Kothapalli ◽  
Mahmoud Elkhooly ◽  
Divyanshu Dubey
Keyword(s):  
Patient Outcomes ◽  
Neurological Disorders ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Management Strategies ◽  
Paraneoplastic Neurological Syndrome ◽  
Paraneoplastic Neurological Syndromes ◽  
Onconeural Antibodies ◽  
Clinical Presentations ◽  
Paraneoplastic Neurological Disorders

We provide an overview of the varied presentations of paraneoplastic neurological syndromes. We also review the onconeural antibodies and their particular oncological and neurological associations. Recognition of these syndromes and their oncological associations is crucial, as early diagnosis and management has been associated with better patient outcomes. Specific management strategies and prognosis vary widely depending on the underlying etiology. An understanding of the relevant clinical details, imaging findings, and other diagnostic information can help tailor treatment approaches. We provide an outline of the diagnostic evaluation and treatment of various paraneoplastic neurological disorders, presenting with central and/or peripheral nervous system involvement. We briefly discuss neurologic immune checkpoint inhibitor-related adverse events, which can occasionally present with paraneoplastic neurological syndrome phenotypes.

scholarly journals Communication with the Migraine Patient

2002 ◽  
Vol 29 (S2) ◽  
pp. S1-S2 ◽  
Author(s):  
W.J. Becker
Keyword(s):  
Patient Outcomes ◽  
Communication Skills ◽  
Migraine Patient ◽  
Laboratory Tests ◽  
Good Communication ◽  
The Past ◽  
Physician Patient Communication ◽  
Physical Findings ◽  
Physician Patient ◽  
Improve Patient

Much has been added to our knowledge of effective physician-patient communication by the research of the past two decades. Good communication skills are especially important for the clinician dealing with a migraine patient, as neither laboratory tests nor diagnostic physical findings are available to assist the physician in diagnosis and treatment. It is important for clinicians to understand that effective communication skills can be taught and learned and that, once mastered, they have the potential to improve patient outcomes.

scholarly journals Cancer Immune Checkpoint Inhibitor Therapy and the Gut Microbiota

2019 ◽  
Vol 18 ◽  
pp. 153473541984637 ◽  
Author(s):  
Arthur E. Frankel ◽  
Sachin Deshmukh ◽  
Amit Reddy ◽  
John Lightcap ◽  
Maureen Hayes ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Molecular Mechanisms ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Host Immune System ◽  
The Past ◽  
Checkpoint Inhibitor Therapy ◽  
Gut Microbial Community ◽  
Generation Sequencing

The past decade has seen tremendous advances in both our understanding of cancer immunosuppressive microenvironments and colonic bacteria facilitated by immune checkpoint inhibitor antibodies and next generation sequencing, respectively. Because an important role of the host immune system is to communicate with and regulate the gut microbial community, it should not come as a surprise that the behavior of one is coupled to the other. In this review, we will attempt to dissect some of the studies demonstrating cancer immunotherapy modulation by specific gut microbes and discuss possible molecular mechanisms for this effect.

scholarly journals Small-molecule P2RX7 activator sensitizes tumor to immunotherapy and vaccinates mouse against tumor re-challenge

2020 ◽  
Author(s):  
Laetitia Douguet ◽  
Serena Janho dit Hreich ◽  
Jonathan Benzaquen ◽  
Laetitia Seguin ◽  
Thierry Juhel ◽  
...  
Keyword(s):  
Small Molecule ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Tumor Regression ◽  
Checkpoint Inhibitor ◽  
Positive Modulator ◽  
Novel Strategy ◽  
Nsclc Patients ◽  
Improve Patient ◽  
Complete Tumor

ABSTRACTOnly a subpopulation of non-small cell lung cancer (NSCLC) patients responds to immunotherapies, highlighting the urgent need to develop new therapeutic strategies to improve patient outcome. We developed a new chemical positive modulator (HEI3090) of the purinergic P2RX7 receptor that potentiates αPD-1 treatment to effectively control the growth of lung tumors in transplantable and oncogene-induced mouse models and triggers long lasting antitumor immune responses. Mechanistically, the molecule stimulates dendritic P2RX7 expressing cells to generate IL-18 which leads to the production of IFN-γ by Natural Killer and CD4+ T cells within tumors. Combined with immune checkpoint inhibitor, the molecule induces a complete tumor regression in 80% of LLC tumor bearing mice. Cured mice are also protected against tumor re-challenge due to a CD8-dependent protective response. Hence, combination treatment of small-molecule P2RX7 activator followed by immune checkpoint inhibitor represents a promising novel strategy that may be active against NSCLC.

scholarly journals Should Colour be Considered as a Significant Design Variable in Foot Orthoses Prescription Writing?

2021 ◽  
Author(s):  
Simon Spooner ◽  
Ian Griffiths
Keyword(s):  
Patient Outcomes ◽  
Design Variable ◽  
Biopsychosocial Model ◽  
Human Life ◽  
Future Research ◽  
Foot Orthoses ◽  
Psychological Responses ◽  
Colour Perception ◽  
Cognition And Emotion ◽  
Improve Patient

Colours act as stimuli capable of inducing physiological and psychological responses, impacting on human life by influencing behaviour, cognition and emotion. Designers frequently draw upon colour association cues in designing products, packaging and marketing materials to exploit the reported human reactions to them. To date, clinicians and foot orthoses manufacturers appear to have given little thought to how the colour of foot orthoses may have impact within the broader context of a biopsychosocial model of healthcare. Here we examine research regarding colour perception and association and provide rationale for how the use of colour in foot orthoses therapy might be better exploited to improve patient outcomes and to form a focus for future research.

scholarly journals Cutaneous Melanoma, Version 2.2019, NCCN Clinical Practice Guidelines in Oncology

2019 ◽  
Vol 17 (4) ◽  
pp. 367-402 ◽  
Author(s):  
Daniel G. Coit ◽  
John A. Thompson ◽  
Mark R. Albertini ◽  
Christopher Barker ◽  
William E. Carson ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Targeted Therapy ◽  
Clinical Practice Guidelines ◽  
Practice Guidelines ◽  
Cutaneous Melanoma ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Distant Metastatic Disease ◽  
Nccn Guidelines ◽  
The Past

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Cutaneous melanoma have been significantly revised over the past few years in response to emerging data on immune checkpoint inhibitor therapies and BRAF-targeted therapy. This article summarizes the data and rationale supporting extensive changes to the recommendations for systemic therapy as adjuvant treatment of resected disease and as treatment of unresectable or distant metastatic disease.

scholarly journals Tyrosine Kinase Inhibitor and Immune Checkpoint Inhibitor Responses in KIT-Mutant Metastatic Melanoma

2019 ◽  
Vol 139 (3) ◽  
pp. 728-731
Author(s):  
Meredith McKean ◽  
Junna Oba ◽  
Junsheng Ma ◽  
Katherine G Roth ◽  
Wei-Lien Wang ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitor ◽  
Metastatic Melanoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Kinase Inhibitor ◽  
Checkpoint Inhibitor

Evaluation and clinical impact of a pharmacist-led, interdisciplinary service focusing on education, monitoring and toxicity management of immune checkpoint inhibitors

2021 ◽  
pp. 107815522110611
Author(s):  
Glenn Myers ◽  
Jonathan Stevens ◽  
Andrew Flewelling ◽  
Jacqueline Richard ◽  
Meagan London
Keyword(s):  
Adverse Event ◽  
Patient Outcomes ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Study Cohort ◽  
Control Cohort ◽  
Related Adverse Event

Introduction Immune-related adverse events are complications of immune checkpoint inhibitors which require robust patient education and proactive follow-up to ensure timely identification and management. Oncology pharmacist practice models with other anticancer modalities have been well documented, but there is limited evidence assessing the spectrum of pharmacist interventions in patients receiving immune checkpoint inhibitor(s) and the impact of these interventions on patient outcomes. Methods Patients initiated on immune checkpoint inhibitor(s) from 1 January 2016 to 31 August 2019 were included for data collection and analysis. Part 1 featured an intensive pharmacist follow-up cohort (study cohort) and summarized pharmacist interventions. Part 2 compared patient outcomes between the study cohort and a standard of care cohort (control cohort) from a different oncology centre. Patient outcomes included emergency department visits not resulting in admission, hospitalizations due to immune-related adverse event(s), immune checkpoint inhibitor cycles received, treatment discontinuation due to immune-related adverse event(s), completion of finite programmed death-1/death-1 ligand treatment course and completion of ipilimumab. Clinical outcomes were compared using a retrospective, matched cohort design based on age, cancer diagnosis and immune checkpoint inhibitor(s). Results A total of 143 patients were included in Part 1 encompassing 1664 pharmacist recommendations across 11 categories. The matched cohort yielded 92 matches (n = 184) with a higher odds of immune checkpoint inhibitor discontinuation due to immune-related adverse event(s) in the control cohort (odds ratio (OR) (95% confidence interval (CI)) = 5.5 (1.2−24.8); p = 0.022). Conclusion Intensive immune-related adverse event education, proactive follow-up and immune-related adverse event management by pharmacists result in clinically meaningful interventions which correlate to improved patient outcomes, namely lower odds of treatment discontinuation due to immune-related adverse event(s).

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