60MO Gut microbiota and efficacy of immune-checkpoint inhibitors (ICIs) in patients (pts) with advanced solid tumor: SCRUM-Japan MONSTAR-SCREEN

: Application of immune checkpoint inhibitors (ICIs) is a major breakthrough in the field of cancer therapy, which has displayed tremendous potential in various types of malignancies. However, their response rates range widely in different cancer types and a significant number of patients experience immune-related adverse effects (irAEs) induced by these drugs, limiting the proportion of patients who can truly benefit from ICIs. Gut microbiota has gained increasing attention due to its emerging role in regulating the immune system. In recent years, numerous studies have shown that gut microbiota can modulate antitumor response, as well as decrease the risk of colitis due to ICIs in patients receiving immunotherapy. The present review analyzed recent progress of relevant basic and clinical studies in this area and explored new perspectives to enhance the efficacy of ICIs and alleviate associated irAEs via manipulation of the gut microbiota.

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Tu1796 ALTERNATION OF GUT MICROBIOTA IN PATIENT WITH IMMUNE CHECKPOINT INHIBITORS

Gastroenterology ◽

10.1016/s0016-5085(20)33584-8 ◽

2020 ◽

Vol 158 (6) ◽

pp. S-1164-S-1165

Author(s):

Yuki Hirata ◽

Hideki Tawa ◽

Yasuyoshi Tanaka ◽

Kazuki Kakimoto ◽

Ken Kawakami ◽

...

Keyword(s):

Gut Microbiota ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors

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Are Long-Chain Polyunsaturated Fatty Acids the Link between the Immune System and the Microbiome towards Modulating Cancer?

Medicines ◽

10.3390/medicines5030102 ◽

2018 ◽

Vol 5 (3) ◽

pp. 102 ◽

Cited By ~ 9

Author(s):

Leodevico Ilag

Keyword(s):

Fatty Acids ◽

Immune System ◽

Gut Microbiota ◽

Polyunsaturated Fatty Acids ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Optimal Level ◽

Common Denominator ◽

Long Chain

Three recent studies revealed synergy between immune-checkpoint inhibitors and the microbiome as a new approach in the treatment of cancer. Incidentally, there has been significant progress in understanding the role of polyunsaturated fatty acids (PUFAs) in modulating cancer and the immune system, as well as in regulating the microbiome. Inflammation seems to be the common denominator among these seemingly unrelated biological entities—immune system, the microbiome, and long-chain polyunsaturated fatty acids (LC-PUFAs). This commentary presents a hypothesis proposing the existence of an optimal level of LC-PUFAs that nurtures the suitable gut microbiota preventing dysbiosis. This synergy between optimal LC-PUFAs and gut microbiota helps the immune system overcome the immunosuppressive tumour microenvironment including enhancing the efficacy of immune checkpoint inhibitors. A model on how LC-PUFAs (such as omega(n)-3 and n-6 fatty acids) forms a synergistic triad with the immune system and the microbiome in regulating inflammation to maintain homeostasis is presented. The principles underlying the hypothesis provide a basis in managing and even preventing cancer and other chronic diseases associated with inflammation.

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Efficacy and immune-related adverse event associations in avelumab-treated patients

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2020-001427 ◽

2020 ◽

Vol 8 (2) ◽

pp. e001427

Author(s):

Karen Kelly ◽

Juliane Manitz ◽

Manish R Patel ◽

Sandra P D’Angelo ◽

Andrea B Apolo ◽

...

Keyword(s):

Solid Tumor ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Cox Model ◽

Safety Data ◽

Time Dependent ◽

Risk Of Death ◽

Link Type ◽

Event Order

BackgroundAdverse events (AEs) of special interest that arise during treatment with immune checkpoint inhibitors, including immune-related AEs (irAEs), have been reported to be associated with improved clinical outcomes. We analyzed patients treated with avelumab from the JAVELIN Solid Tumor and Merkel 200 trials, examining the association between AEs and efficacy while adjusting for confounding factors such as treatment duration and event order.MethodsWe analyzed efficacy and safety data from 1783 patients treated with the programmed death ligand 1 inhibitor avelumab who were enrolled in expansion cohorts of the JAVELIN Solid Tumor and Merkel 200 trials. To analyze the association between irAEs and efficacy with regard to survival, we used a time-dependent Cox model with time-varying indicators for irAEs, as well as multistate models that accounted for competing risks and time inhomogeneity.Results295 patients (16.5%) experienced irAEs and 454 patients (25.5%) experienced infusion-related reactions. There was a reduced risk of death in patients who experienced irAEs compared with those who did not (HR 0.71, 95% CI 0.59 to 0.85) using the time-dependent Cox model. The multistate model did not suggest that the occurrence of irAEs could predict response; however, it predicted a higher chance of irAEs occurring after a response. No association was observed between response and infusion-related reactions.ConclusionsPatients who experience irAEs showed improved survival. Although irAEs are not predictors for response to immune checkpoint inhibitors, increased vigilance for irAEs is needed after treatment with avelumab.Trial registration numbersNCT01772004 and NCT02155647.

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Immunotherapy in Gynecologic Cancers: What We Know Now and Where We Are Headed

American Society of Clinical Oncology Educational Book ◽

10.1200/edbk_237967 ◽

2019 ◽

pp. e126-e140 ◽

Cited By ~ 8

Author(s):

Kimberly Levinson ◽

Oliver Dorigo ◽

Krista Rubin ◽

Kathleen Moore

Keyword(s):

Solid Tumors ◽

Solid Tumor ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Gynecologic Cancer ◽

Hematologic Malignancies ◽

Next Generation ◽

Gynecologic Cancers ◽

Clinical Benefits

Immunotherapy, mainly in the form of immune checkpoint inhibitors (ICIs), has been transformative in both solid tumor and hematologic malignancies. Patients with previously terminal illnesses have experienced profound responses of great durability with these agents, fueling excitement among patients and providers regarding their use. Unfortunately, the gains seen in some solid tumors have not been replicated in a large percentage of patients with gynecologic cancer. This review focuses on the clinical benefits seen to date, toxicities and management when using ICIs, ways to improve prediction of who should receive immunotherapy, and a discussion of next-generation immunotherapy with cellular therapeutics and how these might relate to gynecologic cancers.

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The Emerging Role of the Gut Microbiome in the Cancer Response to Immune Checkpoint Inhibitors: A Narrative Review

Journal of Immunotherapy and Precision Oncology ◽

10.36401/jipo-21-10 ◽

2021 ◽

Author(s):

Ghada Araji ◽

Julian Maamari ◽

Fatima Ali Ahmad ◽

Rana Zareef ◽

Patrick Chaftari ◽

...

Keyword(s):

Gut Microbiota ◽

Gut Microbiome ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Therapeutic Interventions ◽

The Impact ◽

The Relationship ◽

Gut Microbiota Composition

ABSTRACT The discovery of immune checkpoint inhibitors (ICIs) has revolutionized the care of cancer patients. However, the response to ICI therapy exhibits substantial interindividual variability. Efforts have been directed to identify biomarkers that predict the clinical response to ICIs. In recent years, the gut microbiome has emerged as a critical player that influences the efficacy of immunotherapy. An increasing number of studies have suggested that the baseline composition of a patient's gut microbiota and its dysbiosis are correlated with the outcome of cancer immunotherapy. This review tackles the rapidly growing body of evidence evaluating the relationship between the gut microbiome and the response to ICI therapy. Additionally, this review highlights the impact of antibiotic-induced dysbiosis on ICI efficacy and discusses the possible therapeutic interventions to optimize the gut microbiota composition to augment immunotherapy efficacy.

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Immune-related ocular toxicities in solid tumor patients treated with immune checkpoint inhibitors: a systematic review

Expert Review of Anticancer Therapy ◽

10.1080/14737140.2017.1296765 ◽

2017 ◽

Vol 17 (4) ◽

pp. 387-394 ◽

Cited By ~ 59

Author(s):

Omar Abdel-Rahman ◽

Hani Oweira ◽

Ulf Petrausch ◽

Daniel Helbling ◽

Jan Schmidt ◽

...

Keyword(s):

Systematic Review ◽

Solid Tumor ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Tumor Patients

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Hepatocellular Carcinoma Immunotherapy and the Potential Influence of Gut Microbiome

International Journal of Molecular Sciences ◽

10.3390/ijms22157800 ◽

2021 ◽

Vol 22 (15) ◽

pp. 7800

Author(s):

Sally Temraz ◽

Farah Nassar ◽

Firas Kreidieh ◽

Deborah Mukherji ◽

Ali Shamseddine ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Gut Microbiota ◽

Gut Microbiome ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Critical Role ◽

Hepatic Carcinogenesis ◽

Host Metabolism

Disruptions in the human gut microbiome have been associated with a cycle of hepatocyte injury and regeneration characteristic of chronic liver disease. Evidence suggests that the gut microbiota can promote the development of hepatocellular carcinoma through the persistence of this inflammation by inducing genetic and epigenetic changes leading to cancer. As the gut microbiome is known for its effect on host metabolism and immune response, it comes as no surprise that the gut microbiome may have a role in the response to therapeutic strategies such as immunotherapy and chemotherapy for liver cancer. Gut microbiota may influence the efficacy of immunotherapy by regulating the responses to immune checkpoint inhibitors in patients with hepatocellular carcinoma. Here, we review the mechanisms by which gut microbiota influences hepatic carcinogenesis, the immune checkpoint inhibitors currently being used to treat hepatocellular carcinoma, as well as summarize the current findings to support the potential critical role of gut microbiome in hepatocellular carcinoma (HCC) immunotherapy.

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Patterns and outcomes of immune-related adverse events in solid tumor patients treated with immune checkpoint inhibitors in Thailand: a multicenter analysis

BMC Cancer ◽

10.1186/s12885-021-09003-z ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Nuttapong Ngamphaiboon ◽

Suthinee Ithimakin ◽

Teerada Siripoon ◽

Nattaya Sintawichai ◽

Virote Sriuranpong

Keyword(s):

Overall Survival ◽

Multivariate Analysis ◽

Solid Tumor ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Rank Test ◽

Low Grade ◽

Tumor Patients ◽

Multicenter Analysis

Abstract Background Most immune-related adverse event (irAE) patterns and treatment guidelines are based on western clinical data. We evaluated the incidence and patterns of irAEs in patients treated with immune-checkpoint inhibitors (ICI) in Thailand. Methods All solid tumor patients treated with ICIs were retrospectively reviewed in a multicenter analysis. The study aims to evaluate the incidence of irAEs and their characteristics, treatments, outcomes, and impact on survival. All irAEs were graded using the CTCAE version 4.0. Characteristics of irAEs including time to onset, duration of irAEs, specific treatments, and outcomes of irAEs were reviewed. The Chi-square or Fisher’s exact test was used to compare variables. Overall survival (OS) was estimated by the Kaplan-Meier method, and compared by the log-rank test. A p-value < 0.05 was considered statistically significant. Results irAEs of any grade were observed in 98 of 414 patients (24%), whereas grades 3–4 irAEs were observed in 5.6%. The majority of patients (78%) were treated with monotherapy ICI (anti-PD1/PD-L1 92%). The most common all-grade irAEs were hypothyroidism (7.5%), hepatitis (6.5%), and rash (4.8%). Median onset of overall irAEs was 63 days. Pancreatitis and pneumonitis had the earliest onset at 30 and 34 days, respectively. ICIs were rechallenged in 68 of 98 patients with irAE. Eleven of sixty-eight patients (11.2%) with initial irAE had reoccurrence after ICI rechallenge. Based on a multivariate analysis, pre-existing hypothyroidism, ICI used in a clinical trial setting, and combinations of ICI/ICI were independent factors predicting irAE occurrence. Patients with irAE had a statistically significant longer overall survival (OS) when compared to patients without irAE (p = 0.019). A multivariate analysis revealed that occurrence of irAE was an independent prognostic factor for OS (HR 0.70, 95% CI 0.51–0.96; p = 0.028). Conclusion irAE was commonly observed in Thai cancer patients treated with ICIs. Most irAEs were low-grade and manageable. Re-occurrence of irAE after re-challenging ICI was not uncommonly observed. Patients who experienced irAEs might have significantly longer OS compared to patients without irAEs. However, OS in this study should be interpreted with caution since it might be affected by various tumor types, treatment settings, dosing schedule, and ICI combinations.

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