Sarcoidosis Following Anti-PD-1 and Anti-CTLA-4 Therapy for Metastatic Melanoma

Reddy, Swathi B.; Possick, Jennifer D.; Kluger, Harriet M.; Galan, Anjela; Han, Dale

doi:10.1097/cji.0000000000000181

Cited by 40 publications

(21 citation statements)

References 10 publications

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“…Only one other case of brain radiation necrosis associated with SRS and PD-1 blockade has been reported. 16 Radiotherapy did not seem to induce unusual or severe anti-PD-1-related immune-related adverse events in our series, as all have been reported previously, 19 including sarcoidosis 20 and bullous pemphigoid. 21 We also observed vitiligo-like depigmentation after radiotherapy in 16% of our patients, a feature associated with longer survival in advanced melanoma patients treated with immunotherapy.…”

Section: Discussionsupporting

confidence: 81%

Efficacy of combined hypo-fractionated radiotherapy and anti-PD-1 monotherapy in difficult-to-treat advanced melanoma patients

et al. 2018

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Information on the role of radiotherapy in anti-PD-1 monoclonal antibody-treated melanoma patients is limited. We report on a prospective cohort of advanced melanoma patients treated simultaneously with radiotherapy and anti-PD-1 therapy between 01/01/15 and 30/06/16. Tumor evaluations (RECIST 1.1) were performed every 3 months on radiated and non-radiated lesions. Twenty-five advanced melanoma patients (64% AJCC stage IV M1c, 64% on second-line treatment or more, 60% with elevated LDH serum levels) were included. Radiotherapy was performed early (median: 24 days) after the first anti-PD-1 dose in 15 patients with rapidly progressing symptomatic lesion(s) or later (median: 5.4 months) in 10 patients with progressive disease (PD) despite PD-1 blockade. Radiotherapy was limited to one organ in 24 patients and consisted mainly of hypo-fractioned radiotherapy (median dose 26 Gy in 3–5 fractions, 17 patients) or brain radiosurgery (5 patients). Median follow-up after first anti-PD-1 dose was 16.9 m (range 2.7-27.4), with 44% of patients alive at last follow-up. For radiated lesions, rates of complete (CR), partial (PR) responses, stable disease (SD) or PD were 24%, 12%, 24%, and 32%, respectively. For non-radiated lesions, rates of CR, PR, SD, and PD were 20%, 19%, 12%, and 40%, respectively. Responses achieved after radiotherapy for radiated and non-radiated areas were correlated (Pearson correlation r: 0.89, P<0.0001) suggesting an abscopal effect. Five patients with CR remained disease-free after discontinuation of anti-PD-1 for a median of 9.5 months. No unusual adverse event was recorded. Hypo-fractionated radiotherapy may enhance efficacy of anti-PD1 therapy in difficult-to-treat patients. Controlled studies are needed.

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Section: Discussionsupporting

confidence: 81%

Efficacy of combined hypo-fractionated radiotherapy and anti-PD-1 monotherapy in difficult-to-treat advanced melanoma patients

et al. 2018

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“…Several other reports confirm that sarcoid-like reactions induced by ICIs are common and often do not require other treatment than drug discontinuation [ 56 - 58 ], though in some cases ICI-treatment may be continued without a significant impact on the patient’s clinical conditions [ 59 , 60 ].…”

Section: Resultsmentioning

confidence: 99%

Musculoskeletal and Rheumatic Diseases Induced by Immune Checkpoint Inhibitors: A Review of the Literature

Benfaremo

Manfredi

Luchetti

et al. 2018

CDS

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Background: Immune checkpoint inhibitors are a new promising class of antitumor drugs that have been associated with a number of immune-related Adverse Events (AEs), including musculoskeletal and rheumatic disease.Methods: We searched Medline reviewing reports of musculoskeletal and rheumatic AEs induced by immune checkpoint inhibitors.Results: Several musculoskeletal and rheumatic AEs associated with immune checkpoint inhibitors treatment are reported in the literature. In particular, arthralgia and myalgia were the most common reported AEs, whereas the prevalence of arthritis, myositis and vasculitis is less characterized and mainly reported in case series and case reports. Other occasionally described AEs are sicca syndrome, polymyalgia rheumatica, systemic lupus erythematosus and sarcoidosis.Conclusion: Newly induced musculoskeletal and rheumatic diseases are a frequent adverse event associated with immune checkpoint inhibitors treatment

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“…Sarcoidosis has previously been reported as an adverse effect of checkpoint inhibition [ 1 , 2 ]. To date, to the authors’ knowledge, there have not been any reports of sarcoidosis as an IRAE on such a delayed timeline as the one seen in this case report [ 3 , 4 ].…”

Section: Introductionmentioning

confidence: 91%

Delayed onset of neurosarcoidosis after concurrent ipilimumab/nivolumab therapy

Tan

Malinzak

Salama

2018

j. immunotherapy cancer

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BackgroundImmune checkpoint inhibitors have transformed the treatment landscape for many cancers, including metastatic melanoma, but have also opened the door for a diverse variety of immune-related adverse effects.Case presentationWe describe the first reported case of presumed neurosarcoidosis as an immune-related adverse effect that developed nearly a year after discontinuation of treatment with combination ipilimumab and nivolumab for recurrent metastatic melanoma. The patient was noted to develop clinical signs consistent with systemic sarcoidosis shortly after the initiation of treatment and underwent a biopsy of hilar lymphadenopathy that confirmed sarcoidosis and after which immunotherapy was discontinued. His melanoma remained stable on surveillance imaging for the next year after which time he developed neurological symptoms and was found to have MRI brain abnormalities without evidence of intracranial metastatic disease, consistent with probable neurosarcoidosis given biopsy-proven systemic sarcoidosis and lack of evidence of CNS infection or malignancy. He underwent treatment with high dose steroids, followed by infliximab, and then methotrexate with both clinical and radiographic improvement within 4 months of starting treatment.ConclusionsImmune-related adverse effects often occur within 3–6 months of receiving immune checkpoint inhibitor therapy, with some reports of late toxicity. This report highlights a case of probable neurosarcoidosis nearly a year after discontinuation of immune checkpoint therapy. The potential for durable responses after discontinuation of therapy also likely underscores a potential for late toxicity. In patients presenting with new or unexplained symptoms after checkpoint inhibitor therapy, the index of suspicion for an immune-related adverse effect should remain high, irrespective of timing.

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Sarcoidosis Following Anti-PD-1 and Anti-CTLA-4 Therapy for Metastatic Melanoma

Cited by 40 publications

References 10 publications

Efficacy of combined hypo-fractionated radiotherapy and anti-PD-1 monotherapy in difficult-to-treat advanced melanoma patients

Efficacy of combined hypo-fractionated radiotherapy and anti-PD-1 monotherapy in difficult-to-treat advanced melanoma patients

Musculoskeletal and Rheumatic Diseases Induced by Immune Checkpoint Inhibitors: A Review of the Literature

Delayed onset of neurosarcoidosis after concurrent ipilimumab/nivolumab therapy

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