FMT Combined With Immune Checkpoint Inhibitor and TKI in the Treatment of CRC Patients With Advanced Stage
Ontology highlight
ABSTRACT:
DISEASE(S): Colorectal Neoplasms Malignant,Colorectal Neoplasms,Neoplasms
PROVIDER: 2709355 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
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Project description:Interventions: experimental group:Sintilimab combined with Fruquintinib and Fecal Microbiota Transplantation(FMT)
Primary outcome(s): ORR
Study Design: Single arm
| 36777 | ecrin-mdr-crc
Project description:We report the first case series of ICI associated colitis successfully treated with fecal microbiota transplantation (FMT), with reconstitution of the gut microbiome and a relative increase in the proportion of regulatory T cells (Tregs) within the colonic mucosa. These preliminary data provide evidence that modulation of the gut microbiome may abrogate ICI-associated colitis.
| EGAS00001003217 | EGA
Project description:Interventions: Experimental group:Fecal Microbiota Transplantation combined with Immune Checkpoint Inhibitors and Bevacizumab
Primary outcome(s): Changes of intestinal flora quantity;15 immune functions
Study Design: Single arm
| 2761742 | ecrin-mdr-crc
Project description:BACKGROUND:Pneumonitis from immune checkpoint inhibitors (ICI) is a potentially fatal immune-related adverse event (irAE) from antiprogrammed death 1/programmed death ligand 1 immunotherapy. Most cases of ICI pneumonitis improve or resolve with 4-6 weeks of corticosteroid therapy. Herein, we report the incidence, clinicopathological features and management of patients with non-small cell lung cancer (NSCLC) and melanoma who developed chronic ICI pneumonitis that warrants ?12 weeks of immunosuppression. METHODS:Patients with ICI pneumonitis were identified from institutional databases of ICI-treated patients with advanced melanoma and NSCLC between January 2011 and July 2018. ICI pneumonitis was defined as clinical/radiographic evidence of lung inflammation without alternative diagnoses, adjudicated by a multidisciplinary team. Chronic ICI pneumonitis was defined as pneumonitis that persists or worsens with steroid tapering, and necessitates ?12 weeks of immunosuppression, after ICI discontinuation. Serial chest CT was used to assess radiological features, and tumor response by Response EvaluationCriteria for Solid Tumors V.1.1. Bronchoalveolar lavage fluid (BALF) samples were assessed by cell differential. Lung biopsy samples were evaluated by H&E staining and multiplex immunofluorescence (mIF), where available. RESULTS:Among 299 patients, 44 developed ICI pneumonitis (NSCLC: 5/205; melanoma: 1/94), and of these, 6 experienced chronic ICI pneumonitis. The overall incidence of chronic ICI pneumonitis was thus 2%. Of those who developed chronic ICI pneumonitis: the majority had NSCLC (5/6), all sustained disease control from ICIs, and none had other concurrent irAEs. Timing of chronic ICI pneumonitis development was variable (range: 0-50 months), and occurred at a median of 12 months post ICI start. Recrudescence of ICI pneumonitis occurred at a median of 6 weeks after initial steroid start (range: 3-12 weeks), with all patients requiring steroid reintroduction when tapered to ?10 mg prednisone/equivalent. The median total duration of steroids was 37 weeks (range: 16-43+weeks). Re-emergence of radiographic ICI pneumonitis occurred in the same locations on chest CT, in most cases (5/6). All patients who developed chronic ICI pneumonitis had BALF lymphocytosis on cell differential and organising pneumonia on lung biopsy at initial ICI pneumonitis presentation, with persistent BALF lymphocytosis and brisk CD8+ infiltration on mIF at pneumonitis re-emergence during steroid taper. CONCLUSIONS:A subset of patients who develop pneumonitis from ICIs will develop chronic ICI pneumonitis, that warrants long-term immunosuppression of ?12 weeks, and has distinct clinicopathological features.
| S-EPMC7304886 | biostudies-literature
Project description:Side effects of immune checkpoint inhibitors, termed immune-related adverse events, are relatively common, but immune checkpoint inhibitor-mediated cardiotoxicities are rare; however, they can be serious and potentially fatal. Pericarditis is an infrequent cardiac toxicity of immunotherapy and predisposing factors remain unknown. Here we report three patients with NSCLC who developed pericarditis during therapy with programmed death 1/programmed death ligand 1+/- CTLA-4 inhibitors. We review the clinical presentation of these three cases and histopathologic findings from autopsies from the first two patients and a pericardial sampling that has been obtained from a pericardial window procedure in the third patient who recovered from the pericarditis episode. We also discuss the potential mechanisms, as well as what is known about pericarditis secondary to immune-related adverse events.
| S-EPMC6617516 | biostudies-literature
Project description:Commentary on « Ipilimumab induced vasculitis » by Padda A. et al., J Immunother Cancer. 2018;6:12. The authors diagnosed a small vessel vasculitis following treatment with anti-CTLA-4 (ipilimumab) for a resected stage III B/C melanoma. We report a similar case of acral vasculitis occurring with a combination of anti-CTLA-4 (tremelimumab) and anti-PD-L1 (durvalumab) prescribed for the management of a metastatic urothelial bladder cancer. In contrast to Padda A. et al., we observed a significant improvement with oral corticosteroids.
| S-EPMC6240222 | biostudies-literature
Project description:The development of immune checkpoint inhibitors (ICIs) has been a major breakthrough in cancer immunotherapy. The increasing use of ICIs has led to the discovery of a broad spectrum of immune-related adverse events (irAEs). Immune-related myasthenia gravis (irMG) is a rare but life-threatening irAE. In this review, the clinical presentations of irMG are described and the risk of irMG-related mortality is examined using information from relevant studies. In 47 reported cases of irMG with clear causes of mortality, irMG appeared to be a distinct category of neuromuscular disorders and differed from classical MG in terms of its demographic patient characteristics, pathogenesis, serology profile, response to treatment, associated complications, and prognosis. Because of the high mortality of irMG, measures to increase the vigilance of medical teams are necessary to ensure the timely identification of the signs of irMG and early treatment, particularly in the early course of ICI therapy. The diagnostic plans should be comprehensive and include the evaluation of other organ systems, such as the dermatological, gastrointestinal, respiratory, neuromuscular, and cardiovascular systems, in addition to the traditional diagnostic tests for MG. Treatment plans should be individualized on the basis of the extent of organ involvement and clinical severity. Additional therapeutic studies on irMG in the future are required to minimize irAE-related mortality and increase the safety of patients with cancer in the ICI era.
| S-EPMC7378376 | biostudies-literature
Project description:Purpose of reviewImmune checkpoint inhibitor (ICI) therapy revolutionized the treatment of multiple solid and hematologic malignancies. Yet, with it came profound inflammatory toxicities that mimic autoimmune diseases, termed immune-related adverse events (irAEs). Prominent among these is gastrointestinal inflammation, including a spectrum of gastritis, enteritis, and colitis. Here we synthesize an approach to immune checkpoint related enterocolitis (irEC) - including diagnostics and therapeutics - underpinned by new insights into the mechanism behind these phenomena.Recent findingsThis review presents updated insights on how to approach irEC, including novel approaches to selective immunosuppressive therapy, the role of fecal microbiota transplant, and the underlying cellular mechanisms of irEC. This review provides an update on irEC diagnosis and therapy, with considerations of new therapies and special patient populations. The field of gastrointestinal irAEs requires additional investigation, which will ultimately provide the tools required for patients to continue to receive life-saving ICI therapy.
| S-EPMC9583048 | biostudies-literature
Project description: Not available
| S-EPMC8488949 | biostudies-literature
Project description:This study aims to evaluate the efficacy of CVL218 in combination with Toripalimab injection/Sintilimab injection (Darbersol, Sintilimab) in the treatment of advanced solid tumors. It focuses on assessing the safety, tolerability, and pharmacokinetic profile of a three-drug combination regimen comprising albumin-bound paclitaxel injection (Kealil), paclitaxel injection (Taxol), and Fuquinitinib capsule (Aiutec, Fruquintinib).
| 108884 | ecrin-mdr-crc