Drug-induced lupus erythematosus following immunotherapy with anti-programmed death-(ligand) 1

Michot, Jean‐Marie; Fusellier, Mathilde; Champiat, Stéphane; Velter, C.; Baldini, Capucine; Voisin, Anne-Laure; Danlos, François‐Xavier; Dakdouki, Yolla El; Annereau, Maxime; Mariette, Xavier; Robert, Caroline; Cherif, Khadija; Marabelle, Aurélien; Mateus, Christine; Lambotte, Olivier

doi:10.1136/annrheumdis-2018-213677

Cited by 42 publications

(29 citation statements)

References 8 publications

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“…A few cases of lupus-like cutaneous reaction and one Jaccoud arthropathy have yet been reported with anti-PD-1 agents, and only one lupus-like nephritis was attributed to anti-CTLA-4 treatment. [97][98][99][100][101][102] All vessel-sized vasculitis (eg, large, medium and small vessels) with various clinical manifestations, including purpura, digital necrosis arthralgia, arthritis, myalgia, fever, fatigue and abdominal pain have also been reported. 40 48 84 103-113 Of note, ANA, antineutrophil cytoplasmic antibodies (ANCAs), cryoglobulin and RF were rarely positive.…”

Section: Points To Considermentioning

confidence: 99%

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EULAR points to consider for the diagnosis and management of rheumatic immune-related adverse events due to cancer immunotherapy with checkpoint inhibitors

et al. 2020

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BackgroundRheumatic and musculoskeletal immune-related adverse events (irAEs) are observed in about 10% of patients with cancer receiving checkpoint inhibitors (CPIs). Given the recent emergence of these events and the lack of guidance for rheumatologists addressing them, a European League Against Rheumatism task force was convened to harmonise expert opinion regarding their identification and management.MethodsFirst, the group formulated research questions for a systematic literature review. Then, based on literature and using a consensus procedure, 4 overarching principles and 10 points to consider were developed.ResultsThe overarching principles defined the role of rheumatologists in the management of irAEs, highlighting the shared decision-making process between patients, oncologists and rheumatologists. The points to consider inform rheumatologists on the wide spectrum of musculoskeletal irAEs, not fulfilling usual classification criteria of rheumatic diseases, and their differential diagnoses. Early referral and facilitated access to rheumatologist are recommended, to document the target organ inflammation. Regarding therapeutic, three treatment escalations were defined: (1) local/systemic glucocorticoids if symptoms are not controlled by symptomatic treatment, then tapered to the lowest efficient dose, (2) conventional synthetic disease-modifying antirheumatic drugs, in case of inadequate response to glucocorticoids or for steroid sparing and (3) biological disease-modifying antirheumatic drugs, for severe or refractory irAEs. A warning has been made on severe myositis, a life-threatening situation, requiring high dose of glucocorticoids and close monitoring. For patients with pre-existing rheumatic disease, baseline immunosuppressive regimen should be kept at the lowest efficient dose before starting immunotherapies.ConclusionThese statements provide guidance on diagnosis and management of rheumatic irAEs and aim to support future international collaborations.

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Section: Points To Considermentioning

confidence: 99%

“…[98][99][100][101] Subacute cutaneous lupus was mainly treated with topical steroids. 97 Treatment of patients with myositis is reported in a separate statement (point to consider 8).…”

Section: Recommendationmentioning

confidence: 99%

EULAR points to consider for the diagnosis and management of rheumatic immune-related adverse events due to cancer immunotherapy with checkpoint inhibitors

et al. 2020

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“…8 In addition, it was previously reported that among five efficacy evaluable cancer patients with the occurrence of lupus erythematosus after receiving CPIs, three individuals had complete or partial remission and two of them were treated with pembrolizumab. 15 It is impressive that CPI showed remarkable efficacy in this patient with HRD pancreatic cancer carrying two SLE risk alleles, which may inspire future investigation of the intrinsic correlation between efficacy and side effects of checkpoint inhibitors in tumors. Predictive biomarkers of immunotherapy-related toxicity are worth studying, like autoantibodies 16 or genetic factors.…”

Section: Discussionmentioning

confidence: 85%

Durable benefit from immunotherapy and accompanied lupus erythematosus in pancreatic adenocarcinoma with DNA repair deficiency

Pang¹,

Qian²,

Jin³

et al. 2020

J Immunother Cancer

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BackgroundClinical trials showed limited benefit of anti-PD-1 (programmed cell death 1) monotherapy in pancreatic adenocarcinoma patients and immune-related adverse events caused by immune checkpoint inhibitors were rarely reported in pancreatic adenocarcinoma. Here, we report the first case of durable benefit along with systemic lupus erythematosus following immunotherapy in mismatch repair-proficient pancreatic cancer.Case presentationWe describe a 57-year-old woman with resected stage ⅢB pancreatic cancer who underwent several lines of conventional chemotherapy after multiple lymph node metastases. When the disease progressed again, the patient received an off-label treatment with pembrolizumab (100 mg every 3 weeks). After four cycles of immunotherapy treatment, CA19-9 level rapidly decreased to normal and the lymph node metastases reduced dramatically in volume, demonstrating a partial response to the therapy by RECIST 1.1 criteria. She continued on pembrolizumab and a total of eight cycles of administration she had received. Her lesions showed consistent reduction in size even when the medication had been stopped. Actually the patient experienced durable benefit from anti-PD-1 therapy for more than 4 years and she is still in good condition without tumor relapses to date. Besides, she was diagnosed with systemic lupus erythematosus 2 months after the last dose of pembrolizumab. Molecular profiling identified two deleterious PALB2 alterations including a germline mutation (PALB2 c.3114–1G>A) and a somatic mutation (PALB2 c.2514+1G>C) in this patient, suggesting the potential of DNA homologous recombination deficiency. Multiplex immunohistochemistry and RNA-seq results revealed a brisk immune cell infiltration in her resected primary lesion. Additionally, humanleukocyte antigen (HLA) typing assay identified two previously reported systemic lupus erythematosus risk alleles HLA-DRB1*15:01 and HLA-DQB1*06:02 in this patient.ConclusionsThe deleterious mutations of PALB2 closely related to homologous recombination deficiency or alterations of DNA damage response and repair genes might be promising biomarkers for predicting efficacy of immune checkpoint inhibitors in pancreatic adenocarcinoma. Genetic correlation behind immunotherapy-induced systemic lupus erythematosus and associated mechanism remain to be elucidated.

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“…His SCLE has not recurred despite ongoing use of his PPI. Cases of DI-SCLE and drug-induced systemic lupus have been reported with monoclonal antibodies that inhibit programmed death receptor-1 and its ligand, drugs used to treat melanoma 22–24…”

Section: Discussionmentioning

confidence: 99%

Subacute cutaneous lupus erythematosus with a possible paraneoplastic association with melanoma

Hirner

2019

BMJ Case Rep

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A 52-year-old man was referred to our dermatology clinic for a diagnosis of melanoma. At the time, his melanoma was excised he developed an annular, polycyclic, scaling eruption consistent with subacute cutaneous lupus erythematosus (SCLE). Skin biopsy and laboratory evaluation confirmed this diagnosis. The patient had been using pantoprazole for gastro-oesophageal reflux disease for the last 3 years. The patient’s melanoma was treated surgically, and his SCLE was treated with topical steroids and hydroxychloroquine. His SCLE cleared rapidly, his steroids and hydroxychloroquine were stopped and he remains free of SCLE off of treatment. The parallel course of the patient’s SCLE and melanoma prompted consideration of SCLE as paraneoplastic to melanoma in this case. The clinical picture was complicated by the patient’s use of a proton pump inhibitor, which are common causes of drug-induced SCLE. To our knowledge, this is the first reported case of possible paraneoplastic SCLE associated with melanoma.

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Drug-induced lupus erythematosus following immunotherapy with anti-programmed death-(ligand) 1

Cited by 42 publications

References 8 publications

EULAR points to consider for the diagnosis and management of rheumatic immune-related adverse events due to cancer immunotherapy with checkpoint inhibitors

EULAR points to consider for the diagnosis and management of rheumatic immune-related adverse events due to cancer immunotherapy with checkpoint inhibitors

Durable benefit from immunotherapy and accompanied lupus erythematosus in pancreatic adenocarcinoma with DNA repair deficiency

Subacute cutaneous lupus erythematosus with a possible paraneoplastic association with melanoma

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