Hyperacute toxicity with combination ipilimumab (ipi) and anti-PD1 immunotherapy.

Dearden, Helen; Au, Lewis; Wang, Daniel Ying; Zimmer, Lisa; Eroglu, Zeynep; Smith, Jessica L.; Curvietto, Marcello; Khoo, Christine; Atkinson, Victoria; Lo, Serigne; Guminski, Alexander; Long, Georgina V.; Sandhu, Shahneen; Ascierto, Paolo A.; Carlino, Matteo S.; Johnson, Douglas B.; Larkin, James; Menzies, Alexander M.

doi:10.1200/jco.2018.36.15_suppl.9545

Cited by 3 publications

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“…Previously referenced studies in NSCLC and gastrointestinal cancer patients have not demonstrated a relationship between earlier IRAE onset and increased ICI response. A study in melanoma patients also did not demonstrate this relationship [55]. In a retrospective analysis of metastatic melanoma patients receiving combination therapy with anti-PD-1 and anti-CTLA-4 antibodies, 80 patients experienced IRAEs within 21 days.…”

Section: Introductionmentioning

confidence: 99%

Immune-related adverse events and anti-tumor efficacy of immune checkpoint inhibitors

Das

Johnson

2019

j. immunotherapy cancer

753

555

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Although immune checkpoint inhibitors (ICIs) have transformed the treatment landscape for patients with many advanced malignancies, only 15–60% of patients respond, leaving a broad swath of patients who do not derive benefit. Identifying biomarkers to optimally identify patients who will benefit from ICIs is a major research focus for the oncology community. Thus far, predictive biomarker research has focused on tumor signatures such as microsatellite instability, programmed death-ligand 1 (PD-L1) expression and tumor mutational burden; clinical biomarkers have been far less studied. One potential clinical biomarker for ICI response in patients is immune-related adverse event (IRAE) onset.IRAEs are thought to represent bystander effects from activated T-cells and it is plausible that patients responding to ICIs would have greater likelihood of autoimmune toxicities (e.g. due to a more competent/treatment-responsive immune system, or cross-reactivity between tumor and host tissue). Earlier studies in melanoma patients however, suggested no association between IRAE onset and anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibody efficacy. In contrast, a growing body of literature suggests IRAE onset is predictive of anti-programmed cell death protein 1 (PD-1) and anti-PD-L1 antibody response across a variety of solid tumors. Most of these studies report that patients who experienced IRAEs demonstrate marked improvements in progression-free survival, overall survival and overall response rate compared to those lacking toxicity.Key questions regarding the association between IRAE onset and ICI efficacy remain. The most pertinent of these involve whether the association is only relevant for patients treated with anti-PD-1 and anti-PD-L1 antibodies and whether IRAE site, severity, timing of onset and management influence ICI efficacy. Herein, we discuss the seminal studies which have begun to address these questions and have shaped the narrative about the predictive value of IRAE onset for patients on ICIs, in this review.

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Section: Introductionmentioning

confidence: 99%

Immune-related adverse events and anti-tumor efficacy of immune checkpoint inhibitors

Das

Johnson

2019

j. immunotherapy cancer

753

555

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“…Clinical improvement/benefit was demonstrated in 21/22 patients (96%) with one (5%) patient experiencing grade 4 tocilizumab-related toxicity that was not transient or self-limiting. The short time of irAE onset, as well as the number of patients that required hospitalization indicates that this is a unique population of patients with "hyperacute" toxicities (15). Patients were treated either according to immunopathological patterns and existing evidence regarding the underlying toxicity or due to the elevated IL-6 and CRP levels.…”

Section: Discussionmentioning

confidence: 99%

Interleukin-6 blockade for prophylaxis and management of immune-related adverse events in cancer immunotherapy

Dimitriou

Hogan

Menzies

et al. 2021

European Journal of Cancer

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“…In Ricciuti et al, dermatologic and hepatic‐gallbladder reactions did not result in improved overall survival, but pulmonary, endocrine, and gastrointestinal irAEs did in patients with stage IV NSCLC [ 57 ]. Although the timing of irAE onset and immunotherapy response has not been well reported, studies in patients with gastrointestinal cancer, NSCLC, and melanoma have failed to show an association between earlier irAE onset and improved treatment efficacy [ 42 , 58 , 59 ]. Similarly, irAE severity has not affected treatment efficacy outcomes in several studies [ 58 ].…”

Section: Discussionmentioning

confidence: 99%

The Impact of Adverse Events on Health Care Resource Utilization, Costs, and Mortality Among Patients Treated with Immune Checkpoint Inhibitors

George

Bell

Zheng³

et al. 2021

The Oncologist

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Background. We investigated the association between adverse events (AEs) suspected to be immune-related and health care resource utilization, costs, and mortality among patients receiving programmed cell death 1/programmed cell death ligand 1 immune checkpoint inhibitor (ICI) monotherapy for urothelial carcinoma, renal cell carcinoma, non-small cell lung cancer, or Merkel cell carcinoma. Patients and Methods. We conducted a retrospective cohort study using medical and pharmacy claims and enrollment information from U.S. commercial and Medicare Advantage with Part D enrollees in the Optum Research Database from March 1, 2014, through April 30, 2019. Claims were linked with mortality data from the Social Security Death Index and the National Death Index. Eligible patients had at least one ICI claim between September 1, 2014, and April 30, 2019.Results. After adjusting for potential confounding variables, we found patients with AEs had more than double the risk of an inpatient stay (hazard ratio [HR], 2.2; 95% confidence interval [CI], 1.9-2.5) and an 80% higher risk of an emergency visit (HR,

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Hyperacute toxicity with combination ipilimumab (ipi) and anti-PD1 immunotherapy.

Cited by 3 publications

References 0 publications

Immune-related adverse events and anti-tumor efficacy of immune checkpoint inhibitors

Immune-related adverse events and anti-tumor efficacy of immune checkpoint inhibitors

Interleukin-6 blockade for prophylaxis and management of immune-related adverse events in cancer immunotherapy

The Impact of Adverse Events on Health Care Resource Utilization, Costs, and Mortality Among Patients Treated with Immune Checkpoint Inhibitors

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