Clinical characteristics of rheumatic syndromes associated with checkpoint inhibitors therapy

Kostine, Marie; Truchetet, Marie-Élise; Schaeverbeke, Thierry

doi:10.1093/rheumatology/kez295

Cited by 37 publications

(25 citation statements)

References 76 publications

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“…The median time from ICI initiation to symptom onset appears to be less than three months. Joint involvement has been evidenced after only one dose of ICIs but can also occur up to 2 years after immunotherapy, sometimes becoming chronic despite the cessation of ICIs [ 28 ].…”

Section: Rheumatic Immune-related Adverse Eventsmentioning

confidence: 99%

Rheumatic Immune-Related Adverse Events—A Consequence of Immune Checkpoint Inhibitor Therapy

Bobircă

Ancuta

et al. 2021

Biology

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The advent of immunotherapy has changed the management and therapeutic methods for a variety of malignant tumors in the last decade. Unlike traditional cytotoxic chemotherapy, which works by interfering with cancer cell growth via various pathways and stages of the cell cycle, cancer immunotherapy uses the immune system to reduce malignant cells’ ability to escape the immune system and combat cell proliferation. The widespread use of immune checkpoint inhibitors (ICIs) over the past 10 years has presented valuable information on the profiles of toxic adverse effects. The attenuation of T-lymphocyte inhibitory mechanisms by ICIs results in immune system hyperactivation, which, as expected, is associated with various adverse events defined by inflammation. These adverse events, known as immune-related adverse events (ir-AEs), may affect any type of tissue throughout the human body, which includes the digestive tract, endocrine glands, liver and skin, with reports of cardiovascular, pulmonary and rheumatic ir-AEs as well. The adverse events that arise from ICI therapy are both novel and unique compared to those of the conventional treatment options. Thus, they require a multidisciplinary approach and continuous updates on the diagnostic approach and management.

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Section: Rheumatic Immune-related Adverse Eventsmentioning

confidence: 99%

Rheumatic Immune-Related Adverse Events—A Consequence of Immune Checkpoint Inhibitor Therapy

Bobircă

Ancuta

et al. 2021

Biology

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“…Median time to symptom onset following ICI initiation did not exceed the period of three months. Review of the literature, however, highlights the clinical variability of ICI-exposed patients developing arthritis [9,13]. In a recent review of case reports and case series [14], 90 cases of de novo ICI-related arthritis were identified in a period of 18 months.…”

Section: Inflammatory Arthritismentioning

confidence: 99%

“…On the other hand, a de novo condition with features of myopathy/myositis has been described in recent years following ICI therapy in cancer patients [6,9,13]. The differentiation between paraneoplastic and ICI-induced myositis can be sometimes difficult [35].…”

Section: Myositismentioning

confidence: 99%

Rheumatic Manifestations in Patients Treated with Immune Checkpoint Inhibitors

Μελισσαρόπουλος

Klavdianou

Filippopoulou

et al. 2020

IJMS

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Immune checkpoint inhibitors (ICIs) are monoclonal antibodies that activate the immune system, aiming at enhancing antitumor immunity. Their clinical efficacy is well-documented, but the side effects associated with their use are still under investigation. These drugs cause several immune-related adverse events (ir-AEs), some of which stand within the field of rheumatology. Herein, we present a literature review performed in an effort to evaluate all publicly available clinical data regarding rheumatic manifestations associated with ICIs. The most common musculoskeletal ir-AEs are inflammatory arthritis, polymyalgia rheumatica and myositis. Non-musculoskeletal rheumatic manifestations are less frequent, with the most prominent being sicca, vasculitides and sarcoidosis. Cases of systemic lupus erythematosus or scleroderma are extremely rare. The majority of musculoskeletal ir-AEs are of mild/moderate severity and can be managed with steroids with no need for ICI discontinuation. In severe cases, more intense immunosuppressive therapy and permanent ICI discontinuation may be employed. Oncologists should periodically screen patients receiving ICIs for new-onset inflammatory musculoskeletal complaints and seek a rheumatology consultation in cases of persisting symptoms.

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“…The impact of immunotherapy on the bone of patients with PCa has only begun to be explored. It is well established that immune checkpoint inhibitors result in immune‐related rheumatic and musculoskeletal adverse events, such as inflammatory arthritis, arthralgia, and myalgia 77,78 . Yet only recently has a study found that immunotherapies result in SREs.…”

Section: Discussionmentioning

confidence: 99%

Integrating the immune microenvironment of prostate cancer induced bone disease

Ihle

Owens

2020

Molecular Carcinogenesis

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Prostate cancer (PCa) is the most frequently diagnosed cancer for men in the U.S. but does not impede patient survival until the disease is metastatic. Metastatic lesions most frequently occur in the bone, which exhibits a distinct microenvironment of immune and bone cell populations. Advances in the diagnosis and treatment of primary PCa allow for the use of tailored therapeutic approaches based on biomarkers, protein expression, and histopathology. Understanding the molecular and cellular characteristics of primary tumors has advanced therapeutic development and survival for patients with PCa.Personalized medicine has only recently emerged for the treatment of metastatic bone lesions. Tumor induced bone disease (TIBD) in patients with PCa can be classified into lytic, blastic, or mixed pathologies, with most patients exhibiting the blastic phenotype.Progress has been made in treating TIBD, but metastatic PCa has yet to be cured. Immune checkpoint inhibitors have exhibited limited responses in immunosuppressivePCa tumors, but have yet to be assessed in metastatic sites which may be susceptible to an increased inflammatory response. Recent discoveries have uncovered distinct tumor microenvironments (TMEs) of blastic and lytic bone metastases from patients with PCa, identifying actionable targets for therapeutic applications, including immune checkpoint inhibitors and targeted therapeutics. Enrichment for macrophages and T cells in patient samples suggests metastatic sites may be reappraised as immunologically targetable, despite their immunologically "cold" primary tumors. The practice of performing bone biopsies will help identify unique cellular and protein targets in the bone TME that can guide therapy decisions. K E Y W O R D S bone metastasis, immmunotherapy, prostate cancer, tumor microenvironment 1 | PROSTATE CANCER 1.1 | Scope of prostate cancer Prostate cancer (PCa) is the most commonly diagnosed cancer for men in the U.S., accounting for more than one in five new cancer diagnoses. 1 Thanks to early diagnosis and effective treatment options, survival is extremely high at >99% for localized and regional tumors. 2 Of the 191 930 estimated new cases of PCa in the U.S. for 2020, only 33 330 patients are expected to succumb to the disease. 1 However, once distant metastases are present patient with PCa survival drops to 30%, as patients face fewer therapeutic

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Clinical characteristics of rheumatic syndromes associated with checkpoint inhibitors therapy

Cited by 37 publications

References 76 publications

Rheumatic Immune-Related Adverse Events—A Consequence of Immune Checkpoint Inhibitor Therapy

Rheumatic Immune-Related Adverse Events—A Consequence of Immune Checkpoint Inhibitor Therapy

Rheumatic Manifestations in Patients Treated with Immune Checkpoint Inhibitors

Integrating the immune microenvironment of prostate cancer induced bone disease

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