Cancers

Research

Jump to: Review

14 pages, 632 KiB

Open AccessArticle

Studying Outcomes after Steroid-Sparing Immunosuppressive Agent vs. Steroid-Only Treatment for Immune-Related Adverse Events in Non-Small-Cell Lung Cancer (NSCLC) and Melanoma: A Retrospective Case-Control Study

by Sharjeel Syed, Jacobi Hines, Rachel Baccile, Sherin Rouhani and Pankti Reid

Cancers 2024, 16(10), 1892; https://doi.org/10.3390/cancers16101892 - 16 May 2024

Cited by 1 | Viewed by 1705

Abstract

Background: The effects of steroid-sparing immunosuppressive agents (SSIAs), used for the treatment of immune-related adverse events (irAEs), on immune checkpoint inhibitor (ICI) antitumor activity is not well known. We compared tumor outcomes of patients who received corticosteroid monotherapy (CS) versus a corticosteroid plus [...] Read more.

Background: The effects of steroid-sparing immunosuppressive agents (SSIAs), used for the treatment of immune-related adverse events (irAEs), on immune checkpoint inhibitor (ICI) antitumor activity is not well known. We compared tumor outcomes of patients who received corticosteroid monotherapy (CS) versus a corticosteroid plus SSIA (CS-SSIA) for irAE treatment, using statistical methods to address immortal time bias. Methods: We conducted a retrospective case-control study on patients ≥ 18 years with melanoma or non-small-cell lung cancer (NSCLC) treated with ≥1 ICI at a quaternary care center between 1 January 2016 and 11 January 2021. Patients were divided into two cohorts: CS or CS-SSIA. We used propensity score nearest-neighbor matching to match on tumor type, stage, and prior lines of therapy. Primary outcomes were progression-free survival (PFS) and overall survival (OS). Secondary outcomes included the time from the start of the irAE treatment to the irAE resolution. Hazard ratios (HRs) for PFS and OS were calculated using the Cox proportional hazard regression method with both (1) the time to the steroid and SSIA as time-varying covariates and (2) a binary exposure classification not accounting for the time to the treatment. Results: A total of 167 patients were included after matching (132 in the CS cohort and 35 in the CS-SSIA cohort). Sixty-six percent of all the patients had melanoma. The most common irAEs requiring treatment were gastroenterocolitis and hepatitis. In an adjusted analysis not accounting for immortal time bias, there were no significant differences in PFS (HR 0.75, 95% CI [0.46–1.23]) or OS (HR 0.82, 95% CI [0.46–1.47]). In analyses using a time-varying treatment indicator, there was a trend toward improved PFS in patients treated with SSIAs (HR 0.54, CI 0.26–1.10). There was no difference in OS (HR 1.11, CI 0.55–2.23). Patients with melanoma who specifically received infliximab had improved PFS compared to patients with CS only, after adjusting for immortal time bias (HR 0.32, CI 0.24–0.43). Conclusions: The use of SSIAs with CS did not have worse outcomes than CS monotherapy. In melanoma, our findings showed improved PFS for the use of infliximab versus steroid monotherapy for irAEs. Large, prospective, randomized controlled trials are needed to confirm these findings and guide the optimal treatment of irAEs. Full article

(This article belongs to the Special Issue How to Properly Diagnose and Treat Immune-Related Adverse Events during Immunotherapy in Patients with Cancer: Discussion between Specialists)

► Show Figures

Figure 1

12 pages, 777 KiB

Open AccessArticle

Occurrence and Management of Immunotherapy-Associated Adverse Events in Patients with Gynecological Cancers

by Ina Shehaj, Maria Schröder, Valerie Catherine Linz, Slavomir Krajnak, Katrin Almstedt, Kathrin Stewen, Roxana Schwab, Annette Hasenburg, Marcus Schmidt and Anne-Sophie Heimes

Cancers 2024, 16(7), 1371; https://doi.org/10.3390/cancers16071371 - 30 Mar 2024

Cited by 2 | Viewed by 1601

Abstract

Background: Immune checkpoint inhibitors (ICIs) have emerged as an essential therapeutic approach in treating many solid tumors. ICIs enhance the body’s anti-tumor T-cell activity, resulting in a novel spectrum of immunotherapy-related side effects. This novel spectrum of adverse events differs significantly from the [...] Read more.

Background: Immune checkpoint inhibitors (ICIs) have emerged as an essential therapeutic approach in treating many solid tumors. ICIs enhance the body’s anti-tumor T-cell activity, resulting in a novel spectrum of immunotherapy-related side effects. This novel spectrum of adverse events differs significantly from the side effects of conventional chemotherapy. It, therefore, requires special attention in the diagnosis and management of immunotherapy-related adverse events (irAEs). The present study aimed to retrospectively analyze the incidence, diagnosis, and management of irAEs in patients with gynecologic malignancies who received ICIs and to discuss these findings in the context of the recent literature. Methods: In the present retrospective overview, we evaluated patients with gynecologic malignancies (breast, endometrial, cervical, ovarian) who received ICIs with regard to the incidence, type, and time to onset of irAEs. A total of 61 patients treated at the Department of Gynecology and Obstetrics, University Medical Center Mainz, Germany, between 2018 and 2023 were included in the analysis. Results: A total of 32.8% of patients developed an irAE of any grade or type. The median time to irAE was 24 weeks. The most frequently observed irAEs were grade 1 (20%) or 2 (35%). Immunotherapy-related grade 3 or 4 adverse events occurred in 45% of patients (40% grade 3, 5% grade 4). The most common type of irAE in our cohort was hypothyroidism, followed by hepatitis and colitis. Cox regression analysis identified the duration of ICI therapy as the only significant factor influencing the incidence of irAEs (p = 0.004). Conclusion: The broad spectrum of irAEs and the onset time of irAEs are important challenges of therapy with ICIs, requiring proactive monitoring and tailored management strategies to optimize the safety and efficacy of immunotherapy. Full article

(This article belongs to the Special Issue How to Properly Diagnose and Treat Immune-Related Adverse Events during Immunotherapy in Patients with Cancer: Discussion between Specialists)

► Show Figures

Figure 1

22 pages, 1770 KiB

Open AccessArticle

Early Changes in LIPI Score Predict Immune-Related Adverse Events: A Propensity Score Matched Analysis in Advanced Non-Small Cell Lung Cancer Patients on Immune Checkpoint Blockade

by Fabrizio Nelli, Agnese Fabbri, Antonella Virtuoso, Diana Giannarelli, Julio Rodrigo Giron Berrios, Eleonora Marrucci, Cristina Fiore and Enzo Maria Ruggeri

Cancers 2024, 16(2), 453; https://doi.org/10.3390/cancers16020453 - 20 Jan 2024

Viewed by 2317

Abstract

In advanced cancer patients undergoing immune checkpoint blockade, the burden of immune-related adverse events (irAEs) is high. The need for reliable biomarkers for irAEs remains unfulfilled in this expanding therapeutic field. The lung immune prognostic index (LIPI) is a noninvasive measure of systemic [...] Read more.

In advanced cancer patients undergoing immune checkpoint blockade, the burden of immune-related adverse events (irAEs) is high. The need for reliable biomarkers for irAEs remains unfulfilled in this expanding therapeutic field. The lung immune prognostic index (LIPI) is a noninvasive measure of systemic inflammation that has consistently shown a correlation with survival in various cancer types when assessed at baseline. This study sought to determine whether early changes in the LIPI score could discriminate the risk of irAEs and different survival outcomes in advanced non-small cell lung cancer (NSCLC) patients receiving PD-(L)1 blockade-based therapies. We included consecutive patients diagnosed with metastatic NSCLC who received pembrolizumab, nivolumab, or atezolizumab as second-line therapy following platinum-based chemotherapy, or first-line pembrolizumab either alone or in combination with platinum-based chemotherapy. The LIPI score relied on the combined values of derived neutrophil/lymphocyte ratio (dNLR) and lactate dehydrogenase. Their assessment at baseline and after two cycles of treatment allowed us to categorize the population into three subgroups with good (LIPI-0), intermediate (LIPI-1), and poor (LIPI-2) prognosis. Between April 2016 and May 2023, we enrolled a total of 345 eligible patients, 165 (47.8%) and 180 (52.2%) of whom were treated as first- and second-line at our facility, respectively. After applying propensity score matching, we considered 83 relevant patients in each cohort with a homogeneous distribution of all characteristics across the baseline LIPI subgroups. There was a noticeable change in the distribution of LIPI categories due to a significant decrease in dNLR values during treatment. Although no patients shifted to a worse prognosis category, 20 (24.1%) transitioned from LIPI-1 to LIPI-0, and 7 (8.4%) moved from LIPI-2 to LIPI-1 (p < 0.001). Throughout a median observation period of 7.3 (IQR 3.9–15.1) months, a total of 158 irAEs (63.5%) were documented, with 121 (48.6%) and 39 (15.7%) patients experiencing mild to moderate and severe adverse events, respectively. Multivariate logistic regression analysis showed that the classification and changes in the LIPI score while on treatment were independent predictors of irAEs. The LIPI-0 group was found to have significantly increased odds of experiencing irAEs. Following a median follow-up period of 21.1 (95% CI 17.9–25.8) months, the multivariable Cox model confirmed LIPI categorization at any given time point as a significant covariate with influence on overall survival, irrespective of the treatment line. These findings suggest that reassessing the LIPI score after two cycles of treatment could help pinpoint patients particularly prone to immune-related toxicities. Those who maintain a good LIPI score or move from the intermediate to good category would be more likely to develop irAEs. The continuous assessment of LIPI provides prognostic insights and could be useful for predicting the benefit of PD-(L)1 checkpoint inhibitors. Full article

(This article belongs to the Special Issue How to Properly Diagnose and Treat Immune-Related Adverse Events during Immunotherapy in Patients with Cancer: Discussion between Specialists)

► Show Figures

Figure 1

14 pages, 780 KiB

Open AccessArticle

Learning Needs of Patients with Cancer and a Pre-Existing Autoimmune Disease Who Are Candidates to Receive Immune Checkpoint Inhibitors

by Maria A. Lopez-Olivo, Johncy J. Kachira, Maryam Buni, Sang Taek Kim, Huifang Lu, Jean H. Tayar, Gabrielle F. Duhon, Juan I. Ruiz, Clifton O. Bingham III, Cassandra Calabrese, Robert J. Volk and Maria E. Suarez-Almazor

Cancers 2023, 15(15), 4004; https://doi.org/10.3390/cancers15154004 - 7 Aug 2023

Cited by 3 | Viewed by 1809

Abstract

Patients with pre-existing autoimmune disorders and cancer considering immune checkpoint inhibitors (ICIs) need to receive balanced information about the benefits and risk of developing immune-related adverse events (irAEs) and flare-ups of their autoimmune disease. To assess the learning needs of patients with cancer [...] Read more.

Patients with pre-existing autoimmune disorders and cancer considering immune checkpoint inhibitors (ICIs) need to receive balanced information about the benefits and risk of developing immune-related adverse events (irAEs) and flare-ups of their autoimmune disease. To assess the learning needs of patients with cancer and pre-existing autoimmune disease regarding ICI treatment, we interviewed 29 patients with autoimmune disease and cancer from a comprehensive cancer center, of whom 20 had received ICI and 9 were candidates to receive ICI at a US Cancer Center. In-depth semi-structured interviews were conducted from August 2021 and January 2022. Interviewee’s opinions and preferences about content and information delivery methods were collected. We recorded and transcribed interviews and analyzed them using thematic analysis. Half of the participants were female, and their median (SD) age was 62.9 (±10.9) years. The identified health information needs included the following: (1) information on irAEs and autoimmune disease flare-ups; (2) benefits of ICI; (3) ICI mechanism in the context of autoimmune disease; (4) management of flare-ups; (5) reasons for stopping or modifying cancer or autoimmune disease treatment; (6) likelihood of autoimmune disease progression or organ damage; and (7) lifestyle changes that could help avoid irAEs. Patients who had received ICI and those who had not yet received treatment reported similar needs, although patients who had received ICI had more questions about cancer treatment modifications. Patients also expressed the need to better understand when to contact their provider and how to share information with multiple providers. Most patients wanted to receive information in visual formats for review at home and at their own pace. Patients expressed interest in having educational tools to facilitate shared decision-making with their physicians, and they identified several areas of health information concerning therapy with ICI. They also highlighted the importance of communication among their various providers. Full article

(This article belongs to the Special Issue How to Properly Diagnose and Treat Immune-Related Adverse Events during Immunotherapy in Patients with Cancer: Discussion between Specialists)

► Show Figures

Figure 1

Review

Jump to: Research

18 pages, 598 KiB

Open AccessReview

Cancer Therapy-Induced Encephalitis

by Nicolas P. Desbaillets and Andreas F. Hottinger

Cancers 2024, 16(21), 3571; https://doi.org/10.3390/cancers16213571 - 23 Oct 2024

Viewed by 1432

Abstract

Encephalitis associated with cancer therapies is a rare but serious complication that can significantly impact patients’ quality of life and it requires prompt identification and management. Over the past two decades, immunotherapy—particularly immune checkpoint inhibitors—has become a cornerstone of cancer treatment, with up [...] Read more.

Encephalitis associated with cancer therapies is a rare but serious complication that can significantly impact patients’ quality of life and it requires prompt identification and management. Over the past two decades, immunotherapy—particularly immune checkpoint inhibitors—has become a cornerstone of cancer treatment, with up to half of metastatic cancer patients in economically developed countries now receiving these therapies. The widespread adoption of immunotherapy has led to improved survival rates and long-term remissions, even in patients with advanced metastatic disease. However, as immune modulators, these therapies can trigger a range of immune-related adverse events, including a variety of novel neurological toxicities. Among these, encephalitis is of particular concern due to its potential severity, which can compromise treatment outcomes. This review aims to provide a comprehensive overview of the literature on this condition, highlighting optimal diagnostic strategies and management approaches to mitigate the risk of significant morbidity, while also comparing encephalitis induced by immunotherapy with that caused by traditional chemotherapies and targeted oncologic treatments. Full article

(This article belongs to the Special Issue How to Properly Diagnose and Treat Immune-Related Adverse Events during Immunotherapy in Patients with Cancer: Discussion between Specialists)

► Show Figures

Figure 1

30 pages, 10460 KiB

Open AccessReview

by Chiara Pozzessere, Bianca Mazini, Patrick Omoumi, Mario Jreige, Leslie Noirez, Antonia Digklia, François Fasquelle, Christine Sempoux and Clarisse Dromain

Cancers 2024, 16(14), 2585; https://doi.org/10.3390/cancers16142585 - 19 Jul 2024

Cited by 3 | Viewed by 2478

Abstract

Immunotherapy has revolutionized oncology care, improving patient outcomes in several cancers. However, these therapies are also associated with typical immune-related adverse events due to the enhanced inflammatory and immune response. These toxicities can arise at any time during treatment but are more frequent [...] Read more.

Immunotherapy has revolutionized oncology care, improving patient outcomes in several cancers. However, these therapies are also associated with typical immune-related adverse events due to the enhanced inflammatory and immune response. These toxicities can arise at any time during treatment but are more frequent within the first few months. Any organ and tissue can be affected, ranging from mild to life-threatening. While some manifestations are common and more often mild, such as dermatitis and colitis, others are rarer and more severe, such as myocarditis. Management depends on the severity, with treatment being held for >grade 2 toxicities. Steroids are used in more severe cases, and immunosuppressive treatment may be considered for non-responsive toxicities, along with specific organ support. A multidisciplinary approach is mandatory for prompt identification and management. The diagnosis is primarily of exclusion. It often relies on imaging features, and, when possible, cytologic and/or pathological analyses are performed for confirmation. In case of clinical suspicion, imaging is required to assess the presence, extent, and features of abnormalities and to evoke and rule out differential diagnoses. This imaging-based review illustrates the diverse system-specific toxicities associated with immune checkpoint inhibitors and chimeric antigen receptor T-cells with a multidisciplinary perspective. Clinical characteristics, imaging features, cytological and histological patterns, as well as the management approach, are presented with insights into radiological tips to distinguish these toxicities from the most important differential diagnoses and mimickers—including tumor progression, pseudoprogression, inflammation, and infection—to guide imaging and clinical specialists in the pathway of diagnosing immune-related adverse events. Full article

(This article belongs to the Special Issue How to Properly Diagnose and Treat Immune-Related Adverse Events during Immunotherapy in Patients with Cancer: Discussion between Specialists)

► Show Figures

Figure 1

23 pages, 5388 KiB

Open AccessReview

Is ¹⁸F-FDG-PET/CT an Optimal Imaging Modality for Detecting Immune-Related Adverse Events after Immune-Checkpoint Inhibitor Therapy? Pros and Cons

by William Karlsen, Lin Akily, Monika Mierzejewska, Jacek Teodorczyk, Artur Bandura, Renata Zaucha and Wojciech Cytawa

Cancers 2024, 16(11), 1990; https://doi.org/10.3390/cancers16111990 - 24 May 2024

Viewed by 2031

Abstract

Immunotherapy with immune checkpoint inhibitors (ICIs) has revolutionized contemporary oncology, presenting efficacy in various solid tumors and lymphomas. However, ICIs may potentially overstimulate the immune system, leading to immune-related adverse events (irAEs). IrAEs may affect multiple organs, such as the colon, stomach, small [...] Read more.

Immunotherapy with immune checkpoint inhibitors (ICIs) has revolutionized contemporary oncology, presenting efficacy in various solid tumors and lymphomas. However, ICIs may potentially overstimulate the immune system, leading to immune-related adverse events (irAEs). IrAEs may affect multiple organs, such as the colon, stomach, small intestine, kidneys, skin, lungs, joints, liver, lymph nodes, bone marrow, brain, heart, and endocrine glands (e.g., pancreas, thyroid, or adrenal glands), exhibiting autoimmune inflammation. ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) is commonly used in oncology for staging and assessment of therapy responses, but it may also serve as a tool for detecting irAEs. This review aims to present various patterns of metabolic activation associated with irAEs due to ICI treatment, identifiable through ¹⁸F-FDG PET/CT. It describes the advantages of early detection of irAEs, but also presents the challenges in differentiating them from tumor progression. It also delves into aspects of molecular response assessment within the context of pseudoprogression and hyperprogression, along with typical imaging findings related to these phenomena. Lastly, it summarizes the role of functional PET imaging in oncological immunotherapy, speculating on its future significance and limitations. Full article

(This article belongs to the Special Issue How to Properly Diagnose and Treat Immune-Related Adverse Events during Immunotherapy in Patients with Cancer: Discussion between Specialists)

► Show Figures

Graphical abstract

30 pages, 2350 KiB

Open AccessReview

by Silvia Casagrande, Giulia Boscato Sopetto, Giovanni Bertalot, Roberto Bortolotti, Vito Racanelli, Orazio Caffo, Bruno Giometto, Alvise Berti and Antonello Veccia

Cancers 2024, 16(7), 1440; https://doi.org/10.3390/cancers16071440 - 8 Apr 2024

Cited by 5 | Viewed by 4368

Abstract

The landscape of cancer treatment has undergone a significant transformation with the introduction of Immune Checkpoint Inhibitors (ICIs). Patients undergoing these treatments often report prolonged clinical and radiological responses, albeit with a potential risk of developing immune-related adverse events (irAEs). Here, we reviewed [...] Read more.

The landscape of cancer treatment has undergone a significant transformation with the introduction of Immune Checkpoint Inhibitors (ICIs). Patients undergoing these treatments often report prolonged clinical and radiological responses, albeit with a potential risk of developing immune-related adverse events (irAEs). Here, we reviewed and discussed the mechanisms of action of ICIs and their pivotal role in regulating the immune system to enhance the anti-tumor immune response. We scrutinized the intricate pathogenic mechanisms responsible for irAEs, arising from the evasion of self-tolerance checkpoints due to drug-induced immune modulation. We also summarized the main clinical manifestations due to irAEs categorized by organ types, detailing their incidence and associated risk factors. The occurrence of irAEs is more frequent when ICIs are combined; with neurological, cardiovascular, hematological, and rheumatic irAEs more commonly linked to PD1/PD-L1 inhibitors and cutaneous and gastrointestinal irAEs more prevalent with CTLA4 inhibitors. Due to the often-nonspecific signs and symptoms, the diagnosis of irAEs (especially for those rare ones) can be challenging. The differential with primary autoimmune disorders becomes sometimes intricate, given the clinical and pathophysiological similarities. In conclusion, considering the escalating use of ICIs, this area of research necessitates additional clinical studies and practical insights, especially the development of biomarkers for predicting immune toxicities. In addition, there is a need for heightened education for both clinicians and patients to enhance understanding and awareness. Full article

(This article belongs to the Special Issue How to Properly Diagnose and Treat Immune-Related Adverse Events during Immunotherapy in Patients with Cancer: Discussion between Specialists)

► Show Figures

Figure 1

24 pages, 850 KiB

Open AccessReview

Non-Invasive Predictive Biomarkers for Immune-Related Adverse Events Due to Immune Checkpoint Inhibitors

by Ben Ponvilawan, Abdul Wali Khan, Janakiraman Subramanian and Dhruv Bansal

Cancers 2024, 16(6), 1225; https://doi.org/10.3390/cancers16061225 - 20 Mar 2024

Cited by 4 | Viewed by 2875

Abstract

Immune-related adverse events (irAEs) are the most common complication of immune checkpoint inhibitor (ICI) therapy. With the widespread use of ICIs in patients with solid tumors, up to 40% of the patients develop irAEs within five months of treatment, and 11% develop severe [...] Read more.

Immune-related adverse events (irAEs) are the most common complication of immune checkpoint inhibitor (ICI) therapy. With the widespread use of ICIs in patients with solid tumors, up to 40% of the patients develop irAEs within five months of treatment, and 11% develop severe irAEs requiring interventions. A predictive test for irAEs would be a crucial tool for monitoring for complications during and after ICI therapy. We performed an extensive review of potential predictive biomarkers for irAEs in patients who received ICI therapy. Currently, only thyroid-stimulating hormone is utilized in common clinical practice. This is due to the unavailability of commercial tests and unclear predictive values from various studies. Given the lack of single strong predictive biomarkers, some novel approaches using composite scores using genomic, transcriptomics, cytokine levels, or clinical parameters appear appealing. Still, these have yet to be validated and incorporated into clinical practice. Further research conducted to validate the models before implementing them into real-world settings will be of the utmost importance for irAE prediction. Full article

(This article belongs to the Special Issue How to Properly Diagnose and Treat Immune-Related Adverse Events during Immunotherapy in Patients with Cancer: Discussion between Specialists)

► Show Figures

Figure 1

13 pages, 281 KiB

Open AccessReview

The ABC of Immune-Mediated Hepatitis during Immunotherapy in Patients with Cancer: From Pathogenesis to Multidisciplinary Management

by Angioletta Lasagna and Paolo Sacchi

Cancers 2024, 16(4), 795; https://doi.org/10.3390/cancers16040795 - 15 Feb 2024

Cited by 1 | Viewed by 2446

Abstract

Immune-mediated hepatotoxicity (IMH) is not-so-rare complication during treatment with immune checkpoint inhibitors (ICIs). This narrative review aims to report the current knowledge on hepatic immune-related adverse events (irAEs) during immunotherapy from pathogenesis to multidisciplinary management. The majority of cases of IMH are asymptomatic [...] Read more.

Immune-mediated hepatotoxicity (IMH) is not-so-rare complication during treatment with immune checkpoint inhibitors (ICIs). This narrative review aims to report the current knowledge on hepatic immune-related adverse events (irAEs) during immunotherapy from pathogenesis to multidisciplinary management. The majority of cases of IMH are asymptomatic and only a few patients may have clinical conditions. The severity of IMH is usually stratified according to Common Terminology for Clinical Adverse Events (CTCAE) criteria, but these scores may overestimate the clinical severity of IMH compared to the Drug-Induced Liver Injury Network (DILIN) scale. The differential diagnosis of IMH is challenging because the elevated liver enzymes can be due to a number of etiologies such as viral infection, autoimmune and metabolic diseases, liver metastases, biliary diseases, and other drugs. The cornerstones of IMH management are represented by withholding or delaying ICI administration and starting immunosuppressive therapy. A multidisciplinary team, including oncologists, hepatologists, internists, and emergency medicine physicians, is essential for the management of IMH. Full article

(This article belongs to the Special Issue How to Properly Diagnose and Treat Immune-Related Adverse Events during Immunotherapy in Patients with Cancer: Discussion between Specialists)

20 pages, 1939 KiB

Open AccessReview

Sargramostim for Prophylactic Management of Gastrointestinal Immune-Related Adverse Events of Immune Checkpoint Inhibitor Therapy for Cancer

by Michael Dougan, Long H. Nguyen, Elizabeth I. Buchbinder and Hillard M. Lazarus

Cancers 2024, 16(3), 501; https://doi.org/10.3390/cancers16030501 - 24 Jan 2024

Cited by 1 | Viewed by 3447

Abstract

Immune checkpoint inhibitor (ICI) therapy improves outcomes in several cancers. Unfortunately, many patients experience grade 3–4 treatment-related adverse events, including gastrointestinal (GI) toxicities which are common. These GI immune-related adverse events (irAEs) induced by ICIs present significant clinical challenges, require prompt intervention, and [...] Read more.

Immune checkpoint inhibitor (ICI) therapy improves outcomes in several cancers. Unfortunately, many patients experience grade 3–4 treatment-related adverse events, including gastrointestinal (GI) toxicities which are common. These GI immune-related adverse events (irAEs) induced by ICIs present significant clinical challenges, require prompt intervention, and result in treatment delays or discontinuations. The treatment for these potentially severe and even fatal GI irAEs which include enterocolitis, severe diarrhea, and hepatitis may interfere with the anti-cancer approach. Sargramostim (glycosylated, yeast-derived, recombinant human GM-CSF) is an agent that has been used in clinical practice for more than 30 years with a well-recognized safety profile and has been studied in many therapeutic areas. The mechanism of action of sargramostim may treat moderate-to-severe GI irAEs without impairing the anti-cancer therapy. Some early data also suggest a potential survival benefit. Through the differentiation/maturation of monocytes, macrophages, and neutrophils and induction of anti-inflammatory T cell responses, GM-CSF aids in GI homeostasis, mucosal healing, and mucosal immunity. GM-CSF knockout mice are susceptible to severe colitis which was prevented with murine GM-CSF administration. For some patients with GI mucosa and immune cell function impairment, e.g., Crohn’s disease, sargramostim reduces disease severity. In a prospective, randomized study (ECOG 1608), advanced melanoma patients had a reduction in grade 3–5 GI irAEs and less frequent colonic perforation in the sargramostim plus ipilimumab arm compared to ipilimumab alone. Sargramostim continues to be studied with ICIs for the prophylactic management of irAEs while also potentially providing a survival benefit. Full article

(This article belongs to the Special Issue How to Properly Diagnose and Treat Immune-Related Adverse Events during Immunotherapy in Patients with Cancer: Discussion between Specialists)

► Show Figures

Figure 1

13 pages, 744 KiB

Open AccessReview

Key Determinants of Immune-Mediated Adverse Reactions to Oncology Drugs

by Yihan Zhou and Shan Ding

Cancers 2023, 15(23), 5622; https://doi.org/10.3390/cancers15235622 - 28 Nov 2023

Cited by 4 | Viewed by 1923

Abstract

To overcome the epidemiological severity of cancer, developing effective treatments is urgently required. In response, immune checkpoint inhibitors (ICIs) have been revealed as a promising resolution for treatment-resistant cancers across the world. Yet, they have both advantages and disadvantages, bringing therapeutic benefits while [...] Read more.

To overcome the epidemiological severity of cancer, developing effective treatments is urgently required. In response, immune checkpoint inhibitors (ICIs) have been revealed as a promising resolution for treatment-resistant cancers across the world. Yet, they have both advantages and disadvantages, bringing therapeutic benefits while simultaneously inducing toxicity, and in particular, immune-mediated adverse drug reactions (imADRs), to the human body. These imADRs can be pathogenic and sometimes lethal, hampering health prediction and monitoring following the provision of ICI treatment. Therefore, it is necessary to collectively identify the determinant factors that contribute to these imADRs induced by ICIs. This article evaluated treatment-, tumor-, and patient-related determinants, and indicated a research gap for future investigations on the pathogenic mechanism of imADRs and translational conversion of determinants into clinical biomarkers to aid pharmacovigilance and cancer therapies. Full article

(This article belongs to the Special Issue How to Properly Diagnose and Treat Immune-Related Adverse Events during Immunotherapy in Patients with Cancer: Discussion between Specialists)

► Show Figures

Figure 1

Journal Menu

Journal Browser

How to Properly Diagnose and Treat Immune-Related Adverse Events during Immunotherapy in Patients with Cancer: Discussion between Specialists

Share This Special Issue

Special Issue Editors

Special Issue Information

Keywords

Benefits of Publishing in a Special Issue

Published Papers (12 papers)

Research

Review

Further Information

Guidelines

MDPI Initiatives

Follow MDPI