scholarly journals Review of Immune Checkpoint Inhibitors and Radiotherapy Related Skin Toxicities

2021 ◽  
Vol 3 (3) ◽  
pp. 10-19
Author(s):  
Margaret A. Kaszycki ◽  
Jonathan Leventhal
Keyword(s):  
Combination Therapy ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Adverse Reactions ◽  
Checkpoint Inhibitors ◽  
Case Reports ◽  
Stevens Johnson Syndrome ◽  
Radiation Recall ◽  
Skin Reactions ◽  
Cutaneous Adverse Reactions

Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy, and their use in combination with radiation therapy (RT) has become increasingly utilized to optimize positive outcomes. The cutaneous adverse reactions from RT as well as ICIs are both well documented; however, in combination these cutaneous toxicities can be exacerbated. ICIs and RT may work synergistically to create an enhanced immune response against the tumor cells. This synergistic effect has been reported to occur both locally at the site of RT, as well as systemically via an abscopal effect. Fortunately, this combination of treatment does not increase the incidence of cutaneous reactions, although several cases have reported enhanced skin toxicity at the site of RT. RT is thought to create an ‘immunocompromised skin district’ or localized immune dysregulation in irradiated skin. This review summarizes previously published case reports and discusses the cutaneous adverse reactions from ICI and RT combination therapy. Properly identifying ICI and RT induced skin reactions depends on several factors including patient history, sequence of therapies, timing of reaction, and histological findings. Skin reactions from combination therapy can range in severity and include ICI-induced radiation recall dermatitis, as well as uncommon presentations of Stevens-Johnson syndrome, lichen planus, and bullous pemphigoid which are localized to or enhanced within areas of prior radiation exposure. It is important for oncologists and dermatologists alike to be aware of the spectrum of reactions associated with ICI and RT.

scholarly journals Immune Response Checkpoint Inhibitors: New Risks of a New Class of Antitumor Agents

2020 ◽  
Vol 8 (1) ◽  
pp. 9-22
Author(s):  
E. V. Shubnikova ◽  
T. M. Bukatina ◽  
N. Yu. Velts ◽  
D. A. Kaperko ◽  
G. V. Kutekhova
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Adverse Reactions ◽  
Checkpoint Inhibitors ◽  
Malignant Neoplasms ◽  
Endocrine Gland ◽  
Skin Reactions ◽  
Immune Mediated

The introduction into clinical practice of immune checkpoint inhibitors that block cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death protein-1 (PD-1), and programmed cell death ligand-1 (PD-L1), has improved the prognosis of patients with malignant neoplasms of diff erent localisation. The antitumour eff ect of immune checkpoint inhibitors is based on blocking CTLA-4 and PD-1/PD-L1 signaling pathways and enhancing lymphocyte antitumour activity. However, inhibition of immune checkpoints may lead to dysregulation of immune responses and appearance of a new type of adverse reactions resulting from changes in the activity of immunocompetent cells. The aim of the study was to analyse adverse reactions associated with the use of immune checkpoint inhibitors. It was demonstrated that the structure of immune-mediated adverse reactions varied depending on the class of immune checkpoint inhibitors. The incidence of immune-mediated adverse reactions was higher with CTLA-4 inhibitors as compared with PD-1/PD-L1 inhibitors, and increased signifi cantly in the case of combination therapy. The treatment with CTLA-4 inhibitors most often resulted in skin reactions (rash, itching), gastrointestinal tract reactions (diarrhea, colitis), and endocrine gland problems (hypophysitis). The treatment with PD-1 inhibitors most often led to respiratory disorders (pneumonitis), and in some cases to gastrointestinal disorders (diarrhea, colitis), skin reactions (rash, itching), and endocrine gland problems (hypothyroidism), but they were less common. The treatment with PD-L1 inhibitors was associated with the development of pneumonitis. The development of immune-mediated adverse reactions may require discontinuation of treatment and administration of immunosuppressants, therefore early diagnosis and timely treatment of complications are important prerequisites for successful antitumour therapy. Further study of the mechanisms of immune-mediated adverse reaction development will optimise antitumour therapy with immune checkpoint inhibitors. 

Cutaneous Adverse Events of Immune Checkpoint Inhibitors: A Summarized Overview

2019 ◽  
Vol 14 (1) ◽  
pp. 14-20 ◽  
Author(s):  
Kerasia-Maria Plachouri ◽  
Eleftheria Vryzaki ◽  
Sophia Georgiou
Keyword(s):  
Side Effects ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Skin Toxicity ◽  
Maculopapular Rash ◽  
Symptomatic Treatment ◽  
Stevens Johnson Syndrome ◽  
Life Threatening ◽  
Skin Side Effects

Background:The introduction of Immune Checkpoint Inhibitors in the recent years has resulted in high response rates and extended survival in patients with metastatic/advanced malignancies. Their mechanism of action is the indirect activation of cytotoxic T-cells through the blockade of inhibitory receptors of immunomodulatory pathways, such as cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), programmed cell death protein-1 (PD-1) and its ligand (PD-L1). Despite their impressive therapeutic results, they can also induce immune-related toxicity, affecting various organs, including the skin.Objective:To provide an updated summarized overview of the most common immune-mediated cutaneous side effects and their management.Method:English articles derived from the databases PubMed and SCOPUS and published between 2009 and 2018, were analyzed for this narrative review.Results:The most common adverse cutaneous reactions include maculopapular rash, lichenoid reactions, vitiligo and pruritus, with severity Grade 1 or 2. Less frequent but eventually life-threatening skin side effects, including Stevens-Johnson syndrome, Drug Reaction with Eosinophilia and Systemic Symptoms and Toxic Epidermal necrolysis, have also been reported.Conclusion:Basic knowledge of the Immune-Checkpoint-Inhibitors-induced skin toxicity is necessary in order to recognize these treatment-related complications. The most frequent skin side effects, such as maculopapular rash, vitiligo and pruritus, tend to subside under symptomatic treatment so that permanent discontinuation of therapy is not commonly necessary. In the case of life-threatening side effects, apart from the necessary symptomatic treatment, the immunotherapy should be permanently stopped. Information concerning the management of ICIs-mediated skin toxicity can be obtained from the literature as well as from the Summary of Product Characteristics of each agent.

scholarly journals Pan-Cancer Analysis Identifies Liver Metastases as Negative Predictive Factor for Immune Checkpoint Inhibitors Treatment Outcome

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiao-Juan Chen ◽  
Aiqun Ren ◽  
Liang Zheng ◽  
En-Dian Zheng ◽  
Tao Jiang
Keyword(s):  
Combination Therapy ◽  
Liver Metastases ◽  
Predictive Factor ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Intrinsic Resistance ◽  
The Impact ◽  
Pan Cancer ◽  
Negative Predictive Factor

This study aimed to investigate the predictive value of liver metastases (LM) in patients with various advanced cancers received immune-checkpoint inhibitors (ICIs). First, clinical and survival data from a published cohort of 1,661 patients who received ICIs therapy were downloaded and analyzed. Second, a retrospective review of 182 patients with advanced non-small-cell lung cancer (NSCLC) who received PD-1/PD-L1 monotherapy was identified. Third, a meta-analysis of published trials was performed to explore the impact of LM on the efficacy of anti-PD-1/PD-L1 based therapy in advanced lung cancers. Pan-cancer analysis revealed that patients with LM had significantly shorter overall survival (OS) than those without LM (10 vs. 20 months; P < 0.0001). Subgroup analysis showed that the presence of LM was associated with markedly shorter OS than those without LM in ICI monotherapy group (P < 0.0001), but it did not reach the statistical significance in ICI-based combination therapy (P = 0.0815). In NSCLC, the presence of LM was associated with significantly inferior treatment outcomes in both pan-cancer and real-world cohort. Interestingly, ICI-based monotherapy and combination therapy could simultaneously prolong progression-free survival (PFS) and OS than chemotherapy in patients without LM. However, ICI-based monotherapy could not prolong PFS than chemotherapy in patients with LM while ICI-based combination therapy could dramatically prolong both PFS and OS. Together, these findings suggested that the presence of LM was the negative predictive factor in cancer patients received ICIs monotherapy, especially in NSCLC. ICI-based combination therapy might overcome the intrinsic resistance of LM to ICIs while the optimal combinatorial strategies remain under further investigation.

Can radiation-recall predict long lasting response to immune checkpoint inhibitors?

2021 ◽  
Vol 154 ◽  
pp. 125-127
Author(s):  
Eric Deutsch ◽  
Benjamin Besse ◽  
Jérôme Le Pavec ◽  
Cécile Le Péchoux ◽  
Angela Botticella ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Radiation Recall

scholarly journals Challenge of immune-mediated adverse reactions in the emergency department

2019 ◽  
Vol 36 (6) ◽  
pp. 369-377 ◽  
Author(s):  
Gregory A Daniels ◽  
Angela D Guerrera ◽  
Donna Katz ◽  
Jayne Viets-Upchurch
Keyword(s):  
Immune System ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Adverse Reactions ◽  
Checkpoint Inhibitors ◽  
Immune Checkpoints ◽  
High Dose ◽  
Clear Understanding ◽  
Immune Mediated ◽  
Multiple Drugs

Multiple drugs of a new class of cancer treatments called immune checkpoint inhibitors, which work by enabling the immune system to attack tumour cells, have been approved for a variety of indications in recent years. Immune checkpoints, such as cytotoxic T-lymphocyte antigen-4 and programmed death-1, are part of the normal immune system and regulate immune activation. Treatment with inhibitors of these checkpoints can significantly improve response rates, progression-free survival and overall survival of patients with cancer; it can also result in adverse reactions that present similarly to other conditions. These immune-mediated adverse reactions (IMARs) are most commonly gastrointestinal, respiratory, endocrine or dermatologic. Although patients’ presentations may appear similar to other types of cancer therapy, the underlying causes, and consequently their management, may differ. Prompt recognition is critical because, with appropriate management, most IMARs resolve and patients can continue receiving immune checkpoint inhibitor treatment. Rarely, these IMARs may be life-threatening and escape detection from the usual evaluations in the emergency environment. Given the unusual spectrum and mechanism of IMARs arising from immune checkpoint inhibitors, emergency departmentED staff require a clear understanding of the evaluation of IMARs to enable them to appropriately assess and treat these patients. Treatment of IMARs, most often with high-dose steroids, differs from chemotherapy-related adverse events and when possible should be coordinated with the treating oncologist. This review summarises the ED presentation and management of IMARs arising from immune checkpoint inhibitors and includes recommendations for tools and resources for ED healthcare professionals.

scholarly journals Successful Treatment of a Patient with anti-PD1 Antibody-Resistant Advanced Mucosal Melanoma with Nivolumab, Ipilimumab plus Denosumab Combination Therapy

2020 ◽  
Vol 13 (1) ◽  
pp. 271-275 ◽  
Author(s):  
Taku Fujimura ◽  
Yumi Kambayashi ◽  
Kentaro Ohuchi ◽  
Ryo Amagai ◽  
Yota Sato ◽  
...  
Keyword(s):  
Malignant Melanoma ◽  
Combination Therapy ◽  
Nasal Cavity ◽  
Immune Checkpoint ◽  
Cutaneous Melanoma ◽  
Japanese Population ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Mucosal Melanoma ◽  
Mutation Burden

Since the incidence of mucosal melanoma is higher in the Japanese population compared to Caucasians, and since mucosal melanoma possesses a lower mutation burden compared to cutaneous melanoma, the efficacy of anti-PD1 antibody (Ab) monotherapy for mucosal melanoma is limited. Therefore, other targeting molecules that enhance the anti-tumor effects of immune checkpoint inhibitors are needed. In this report, we present a case with anti-PD1 Ab-resistant recurrent malignant melanoma of the nasal cavity successfully treated with nivolu­mab, ipilimumab plus denosumab combination therapy.

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