Antiphospholipid syndrome associated with combined immune checkpoint inhibitor therapy

Gupta, Arjun; Shah, Udayan K.; Khine, Htet; Vandergriff, Travis; Froehlich, Thomas

doi:10.1097/cmr.0000000000000335

Cited by 14 publications

(8 citation statements)

References 17 publications

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“…Only one patient with APS induced by ICI therapy has been reported [103]. A 62-year-old male with metastatic melanoma presented with violaceous patches over the palms and planter surfaces of feet with gangrenous tips of fingers and toes after receiving a combination of ipilimumab and nivolumab, thrombotic occlusion of several arterioles in the dermis and elevated anti-β-2 glycoprotein 1 antibodies (immunoglobulin M isotype).…”

Section: Other Rheumatic Immune-related Adverse Eventsmentioning

confidence: 99%

Frequency and distribution of various rheumatic disorders associated with checkpoint inhibitor therapy

Abdel-Wahab

Suarez‐Almazor

2019

Rheumatology

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Immune checkpoint inhibitors have advanced the treatment paradigm of various cancers, achieving remarkable survival benefits. However, a myriad of immune-related adverse events (irAE) has been recognized in almost every organ system, presumably because of persistent immune system activation. Rheumatic symptoms such as arthralgia or myalgia are very common. More specific irAE are increasingly being reported. The most frequent ones are inflammatory arthritis, polymyalgia-like syndromes, myositis and sicca manifestations. These rheumatic irAE can develop in ∼5–10% of patients treated with immune checkpoint inhibitors, although true incidence rates cannot be estimated given the lack of prospective cohort studies, and likely underreporting of rheumatic irAE in oncology trials. In this review, we will provide a summary of the epidemiologic data reported for these rheumatic irAE, until more robust prospective longitudinal studies become available to further define the true incidence rate of rheumatic irAE in patients receiving these novel cancer therapies.

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Section: Other Rheumatic Immune-related Adverse Eventsmentioning

confidence: 99%

Frequency and distribution of various rheumatic disorders associated with checkpoint inhibitor therapy

Abdel-Wahab

Suarez‐Almazor

2019

Rheumatology

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“…16,87 Moreover, whether the presence of aPL antibodies could increase the risk of developing immune-related adverse events in cancer patients treated with immunotherapies is still undetermined. Two patients with aPL antibodies induced by the use of checkpoint inhibitors have been reported, 1 with APS and the other without clinical manifestations 88,89 In addition, aPL antibodies were observed in 18 of 30 patients with melanoma treated with interferon a and/or interleukin-2. 46 Our review included an extensive search of 5 databases and specific criteria for inclusion and quality appraisal.…”

Section: Discussionmentioning

confidence: 99%

Systematic review of observational studies reporting antiphospholipid antibodies in patients with solid tumors

et al. 2020

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This review summarizes the evidence on antiphospholipid (aPL) antibodies and related thromboembolic events in patients with solid tumors. Data sources included Medline, EMBASE, Web of Science, PubMed ePubs, and the Cochrane Central Register of Controlled Trials through August 2019 without restrictions. Observational studies that evaluated patients with solid tumors for the presence of aPL antibodies were included. Data were extracted and quality was assessed by one reviewer and cross-checked by another. Thirty-three studies were identified. Gastrointestinal (GI) and genitourinary (GU) cancers were the most frequently reported. Compared with healthy patients, patients with GI cancer were more likely to develop anticardiolipin antibodies (risk ratio [RR], 5.1; 95% confidence interval [CI], 2.6-9.95), as were those with GU (RR, 7.3; 95% CI, 3.3-16.2) and lung cancer (RR, 5.2; 95% CI, 1.3-20.6). The increased risk for anti-β2-glycoprotein I or lupus anticoagulant was not statistically significant. Patients with lung cancer who had positive aPL antibodies had higher risk of developing thromboembolic events than those who had negative antibodies (RR, 3.8%; 95% CI, 1.2-12.2), while the increased risk in patients with GU cancer was not statistically significant. Deaths due to thromboembolic events were more common among patients with lung cancer who had elevated aPL antibodies. A limitation of this review is that the results are contingent on the reported information. We found an increased risk of developing aPL antibodies in patients with GI, GU, and lung cancers resulting in thromboembolic events and death. Further studies are needed to better understand the pathogenesis and development of aPL antibodies in cancer.

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“…In a literature search, we found three case reports of APS and the use of checkpoint inhibitors. [12][13][14] However, no cases are reported with catastrophic APS following the use of immune checkpoint inhibitors. This might be explained by the scarcity of CAPS in general, the relatively recent introduction of monoclonal antibody against PD-1 in larger patient groups, or by the fact that it is very difficult to diagnose (C)APS properly in patients who already developed multiple organ failure.…”

Section: Discussion (Catastrophic) Antiphospholipid Syndrome and Immumentioning

confidence: 99%

Severe mesenteric ischemia with multiple organ failure in a patient previously treated with a humanized monoclonal antibody against programmed death receptor-1 (pembrolizumab), a case of pembrolizumab associated catastrophic antiphospholipid syndrome?

Mintjens-Jager

Vos

Kats-Ugurlu

et al. 2020

SAGE Open Medical Case Reports

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Immune checkpoint inhibitors are used in the treatment of different types of tumors including melanoma and non-small cell lung carcinoma. The use of these inhibitors is associated with a broad spectrum of immune-related adverse effects. Here we report a case of a patient admitted to the intensive care unit with multiple organ failure due to catastrophic antiphospholipid syndrome following treatment with pembrolizumab, an immune checkpoint inhibitor, because of metastatic melanoma. The presented patient had multiple organ failure of lung, gastro-intestinal, renal, and the liver. Vascular thrombosis was confirmed by both imaging (pulmonary embolism on computed tomography–thorax) and histopathological examination of the intestines. In combination with the presence of IgA anti-cardiolipin antibodies and initially IgM anti-cardiolipin antibodies, catastrophic antiphospholipid syndrome was suspected. Despite treatment with plasmapheresis and corticosteroids, the patient died due to multiple organ failure. Catastrophic antiphospholipid syndrome is difficult to recognize and has high mortality rates despite supportive treatment. In this case report, discussion is provided regarding the possible immunological mechanism behind catastrophic antiphospholipid syndrome during or after treatment with immune checkpoint inhibitors. It is important to realize that in modern intensive care unit, more patients with immune-related adverse effects of the treatment with immune checkpoint inhibitors will be admitted, because of an increase in the number of patients treated with these checkpoint inhibitors. When these patients are admitted on the intensive care unit, multi-disciplinary consultation is important because of the difficulty of early recognition and optimal treatment of these possible lethal side effects.

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Antiphospholipid syndrome associated with combined immune checkpoint inhibitor therapy

Cited by 14 publications

References 17 publications

Frequency and distribution of various rheumatic disorders associated with checkpoint inhibitor therapy

Frequency and distribution of various rheumatic disorders associated with checkpoint inhibitor therapy

Systematic review of observational studies reporting antiphospholipid antibodies in patients with solid tumors

Severe mesenteric ischemia with multiple organ failure in a patient previously treated with a humanized monoclonal antibody against programmed death receptor-1 (pembrolizumab), a case of pembrolizumab associated catastrophic antiphospholipid syndrome?

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