Immunotherapy of cancer with checkpoint inhibitors has been associated with a spectrum of autoimmune and systemic inflammatory reactions known as immune-related adverse events (irAEs). Rheumatic irAEs are infrequently reported and extensively described. Here, we report our experience over an 18-month period with 15 patients evaluated in the rheumatology department for rheumatic irAEs. We identified 13 patients without pre-existing autoimmune disease (AID) who subsequently developed rheumatic irAEs, and two with established AID referred pre-emptively. irAEs encountered included: inflammatory arthritis, sicca syndrome, polymyalgia rheumatica-like symptoms and myositis. All cases required glucocorticoids, and three required a biological agent. Rheumatic irAEs led to temporary or permanent cessation of immunotherapy in all but five patients. One patient with pre-existing AID experienced a flare after starting immunotherapy. Our findings underscore that rheumatic irAEs are complex, at times require additional immunosuppressive therapy, and may influence ongoing immunotherapy regimens for the primary disease. Similar irAEs will be increasingly seen as checkpoint inhibitors adopted as standard of care in the community.
Last. Inge Marie Svane(UCPH: University of Copenhagen)H-Index: 58
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Patients with preexisting active autoimmune disorders were excluded from clinical trials of immune checkpoint inhibitors. However, patients with autoimmune disorders are diagnosed with cancer at least as frequently as the global population, and clinicians treating patients outside clinical trials have generally been reluctant to offer cancer immunotherapy to this patient group. In this brief article, we review the most recent literature on the efficacy and safety of CTLA-4- and PD-1-blocking ant...
Objectives Immune checkpoint inhibitors (ICIs) targeting the cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1) pathways have demonstrated survival improvements in multiple advanced cancers, but also cause immune-related adverse events (IRAEs). IRAEs with clinical features similar to rheumatic diseases have not been well described. We report patients with inflammatory arthritis and sicca syndrome secondary to ICIs. Methods We report patients evaluated...
Immune checkpoint inhibitors have improved clinical outcomes associated with numerous cancers, but high-grade, immune-related adverse events can occur, particularly with combination immunotherapy. We report the cases of two patients with melanoma in whom fatal myocarditis developed after treatment with ipilimumab and nivolumab. In both patients, there was development of myositis with rhabdomyolysis, early progressive and refractory cardiac electrical instability, and myocarditis with a robust pr...
Immune checkpoint inhibition is a novel approach to cancer treatment with enormous potential to improve the outcomes of patients with a range of malignancies. However, owing to this novel approach, a range of adverse events have emerged with different aetiologies to those of more conventional cancer treatments. In this Review, the authors describe the occurrence, and optimal management of adverse events resulting from use of immune checkpoint inhibitors.
Last. Joseph I. Clark(Loyola University Medical Center)H-Index: 35
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Importance Ipilimumab and other immune therapies are effective treatment options for patients with advanced melanoma but cause frequent immune-related toxic effects. Autoimmune diseases are common, and the safety and efficacy of ipilimumab therapy in patients with preexisting autoimmune disorders is not known. Objective To determine the safety and efficacy of ipilimumab therapy in patients with advanced melanoma with preexisting autoimmune disorders. Design, Setting, and Participants Retrospecti...
Cancer immunotherapy is coming of age; it has prompted a paradigm shift in oncology, in which therapeutic agents are used to target immune cells rather than cancer cells. The first generation of new immunotherapies corresponds to antagonistic antibodies that block specific immune checkpoint molecules cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), programmed cell death protein (PD-1) and its ligand PD-L1. Targeting these checkpoints in patients living with cancer had led to long-lasting tu...
Purpose Ipilimumab is a standard treatment for metastatic melanoma, but immune-related adverse events (irAEs) are common and can be severe. We reviewed our large, contemporary experience with ipilimumab treatment outside of clinical trials to determine the frequency of use of systemic corticosteroid or anti-tumor necrosis factor α (anti-TNFα) therapy and the effect of these therapies on overall survival (OS) and time to treatment failure (TTF). Patients and Methods We reviewed retrospectively th...
#1Suzanne L. Topalian(JHUSOM: Johns Hopkins University School of Medicine)H-Index: 99
#2Charles G. Drake(JHUSOM: Johns Hopkins University School of Medicine)H-Index: 89
Last. Drew M. Pardoll(JHUSOM: Johns Hopkins University School of Medicine)H-Index: 142
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The immune system recognizes and is poised to eliminate cancer but is held in check by inhibitory receptors and ligands. These immune checkpoint pathways, which normally maintain self-tolerance and limit collateral tissue damage during anti-microbial immune responses, can be co-opted by cancer to evade immune destruction. Drugs interrupting immune checkpoints, such as anti-CTLA-4, anti-PD-1, anti-PD-L1, and others in early development, can unleash anti-tumor immunity and mediate durable cancer r...
Background Programmed death 1 (PD-1) protein, a T-cell coinhibitory receptor, and one of its ligands, PD-L1, play a pivotal role in the ability of tumor cells to evade the host's immune system. Blockade of interactions between PD-1 and PD-L1 enhances immune function in vitro and mediates antitumor activity in preclinical models. Methods In this multicenter phase 1 trial, we administered intravenous anti–PD-L1 antibody (at escalating doses ranging from 0.3 to 10 mg per kilogram of body weight) to...
Background Blockade of programmed death 1 (PD-1), an inhibitory receptor expressed by T cells, can overcome immune resistance. We assessed the antitumor activity and safety of BMS-936558, an antibody that specifically blocks PD-1. Methods We enrolled patients with advanced melanoma, non–small-cell lung cancer, castrationresistant prostate cancer, or renal-cell or colorectal cancer to receive anti–PD-1 antibody at a dose of 0.1 to 10.0 mg per kilogram of body weight every 2 weeks. Response was as...
Cancer immunotherapy, which seeks to stimulate a patient's own immune system to combat cancer, is quickly becoming a central pillar of cancer therapeutics and has resulted in the development of many novel anticancer therapies. One subtype of cancer immunotherapy, immune checkpoint inhibitors (ICIs), have revolutionized cancer treatment and changed the standard of care for multiple indications. However, the advent of ICIs has produced a wide variety of inflammatory side effects termed immune-rela...
#1Ioana Creţu(UMFCD: Carol Davila University of Medicine and Pharmacy)
#2Mihai Bojincă(UMFCD: Carol Davila University of Medicine and Pharmacy)H-Index: 5
Last. Ruxandra Ionescu(UMFCD: Carol Davila University of Medicine and Pharmacy)H-Index: 20
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Immunotherapy has revolutionized cancer treatment. Immune checkpoint inhibitors (ICIs) including antibodies targeting cytotoxic T lymphocyte associated antigen-4 and programmed cell death 1 have been shown to be effective in the treatment of certain types of cancer. The benefit of these therapies is to prolong life expectancy in the case of metastatic malignancies. Rheumatic adverse events are not very common. In the present study, 9 patients were monitored between November 2018 and January 2020...
Resume Les immunotherapies anti-cancereuses modifient considerablement le pronostic et la prise en charge des patients. En monotherapie ou en association, les inhibiteurs de points de controle de la reponse immunitaire (ICI), anti-CTLA-4 et anti-PD-(L)1 notamment, agissent en inhibant l’immunotolerance tumorale des lymphocytes T ou en stimulant leur action contre les cellules cancereuses. Ce changement de cible therapeutique entraine un profil de toxicite inedit avec l’apparition de complication...
#1Hui Zhong(Peking Union Medical College Hospital)H-Index: 2
#2Jiaxin Zhou(Peking Union Medical College Hospital)H-Index: 9
Last. Xiaofeng Zeng(Peking Union Medical College Hospital)H-Index: 34
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Immune checkpoint inhibitors (ICIs) block the major inhibitory pathways in T cells, resulting in an augmented antitumor response. Immune-related adverse events (irAEs) are a new class of side effects caused by ICIs and tend to be more prevalent in patients with preexisting autoantibodies and autoimmune diseases. The rheumatic subset of irAEs mainly includes arthralgia, arthritis, myalgia, myositis, vasculitis, sicca syndrome, scleroderma and systemic lupus erythematosus. The most common classifi...
Immune-checkpoint inhibitors (ICIs) represent a major development in cancer therapy. The indications for these agents continue to expand across malignancies and disease settings. For years breast cancer (BC) has been considered immunologically quiescent compared with other tumor types. However, recent findings highlighted the immunogenicity of some BCs and paved the way for clinical trials of immunotherapy in BC that led to recent landmark approvals. As a drawback, the safety profile of ICIs is ...
Abstract A 79-year-old woman was diagnosed with stage IV (cT1aN1M1, OSS) lung adenocarcinoma with bone metastasis of the right femur. She received nivolumab as a third-line treatment. She developed pain in the right shoulder, left wrist, right knee, and waist as well as a low-grade fever and morning stiffness, after five courses of nivolumab. After closer examination, she was diagnosed with polymyalgia rheumatica (PMR) precipitated by an immune-related adverse event. Nivolumab was discontinued, ...
Immune checkpoint inhibitor (ICI) medications have seen expanded use in the management of numerous malignancies. These therapies encompass a unique spectrum of immune-related adverse events (irAEs). Rheumatological irAEs from ICIs have been described in various case reports; however, limited literature exists regarding the treatment of patients with pre-existing myositis. We describe a case of myositis flare after initiation of nivolumab for metastatic melanoma in a patient who had previously ac...
Rheumatologists increasingly receive consults for patients treated with immune checkpoint inhibitors (ICIs) for cancer. ICIs can cause inflammatory syndromes known as immune-related adverse events (IRAEs). Several rheumatic IRAEs have been reported, including inflammatory arthritis, polymyalgia rheumatica, and myositis. For patients who present with musculoskeletal symptoms while receiving ICI therapy, it is important to have an algorithm for evaluation. The differential diagnosis includes a ran...
#1Jee Hye Kang(UCSF: University of California, San Francisco)H-Index: 1
#2Jeffrey A. Bluestone(UCSF: University of California, San Francisco)H-Index: 157
Last. Arabella Young(UCSF: University of California, San Francisco)H-Index: 20
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Cancer immunotherapies can successfully activate immune responses towards certain tumors. However, this can also result in the development of treatment-induced immune-related adverse events (irAEs) in multiple tissues. Growing evidence suggests that cytokine production in response to these therapeutics potentiates the development of irAEs and may have predictive value as biomarkers for irAE occurrence. In addition, therapeutic agents that inhibit cytokine activity can limit the severity of irAEs...