Drug-induced sarcoidosis-like reaction in adjuvant immunotherapy: Increased rate and mimicker of metastasis

Chorti, Eleftheria; Kanaki, Theodora; Zimmer, Lisa; Hadaschik, Eva; Ugurel, Selma; Gratsias, Emmanouil; Roesch, Alexander; Bonella, Francesco; Wessendorf, Thomas; Wälscher, Julia; Theegarten, Dirk; Schadendorf, Dirk; Livingstone, Elisabeth

doi:10.1016/j.ejca.2020.02.024

Cited by 55 publications

(58 citation statements)

References 26 publications

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“…However, in the context of life‐saving drugs such as ICIs, this strategy is undesirable. An additional clue favoring the diagnosis of drug‐induced toxicity can be the temporal coincidence of the two events, as in our individual 3 …”

Section: Discussionmentioning

confidence: 81%

Challenges in sarcoidosis and sarcoid‐like reactions associated to immune checkpoint inhibitors: A narrative review apropos of a case

Apalla

Kemanetzi

Papageorgiou

et al. 2020

Dermatologic Therapy

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Sarcoidosis and sarcoid‐like reactions (SLRs) may develop in association with various malignancies, as well as in association to certain oncologic drugs, including immune checkpoint inhibitors (ICIs). We aimed to perform a narrative review with regard to the development of ICIs‐associated sarcoidosis or SLRs, and to discuss the corresponding diagnostic and therapeutic challenges raised in this scenario. Apropos of a melanoma patient developing SLRs while treated with ipilimumab and nivolumab, we searched for clinically evident, ICIs‐associated sarcoidosis or SLRs in the English literature. We recorded the oncologic characteristics, including type of malignancy and type of ICI, the phenotypic characteristics of sarcoidosis/SLRs, as well as the impact on immunotherapy. Including our patient, we identified 80 ICIs‐associated sarcoidosis or SLRs cases. Both sexes were equally affected (40 F/40 M) and the most common malignancy was melanoma (65/80, 81.3%). Concerning the oncologic treatment, there was a predilection for pembrolizumab (23/80, 28.7%), followed by the ipilimumab/nivolumab combination (21/80, 26.3%), ipilimumab (18/80, 22.5%), nivolumab (16/80, 20.0%). Although in the majority of the cases (52/80, 65.0%) there was no need for systemic prednisolone for the management of sarcoidosis, a significant proportion of patients finally discontinued ICIs treatment (44/80, 55.0%). Phenotypically, sarcoidosis and SLRs highly imitate oncologic progression posing diagnostic difficulties. A therapeutic dilemma is also raised when there is a need for systemic prednisolone, since the latter may jeopardize the therapeutic efficacy of immunotherapy. Sarcoidosis and SLRs, though rare, can present in oncologic patients treated with ICIs. Clinicians should be aware of this possibility and the related diagnostic and therapeutic challenges they have to face in this scenario.

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Section: Discussionmentioning

confidence: 81%

Challenges in sarcoidosis and sarcoid‐like reactions associated to immune checkpoint inhibitors: A narrative review apropos of a case

Apalla

Kemanetzi

Papageorgiou

et al. 2020

Dermatologic Therapy

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“…PD-1/programmed death-ligand 1 (PD-L1) inhibition sometimes complicates granuloma formation disorders, including sarcoid reaction and exacerbation of tuberculosis. 7,8 SSG formation appears to be a more frequent event than these granuloma-forming adverse events. Granuloma formation after ICI administration can be attributed to a cellular immunity mechanism similar to that in mycobacterium tuberculosis infection.…”

Section: Discussionmentioning

confidence: 88%

“…We identified SSG as a novel feature that was specific to colon tissue after ICI administration. PD‐1/programmed death‐ligand 1 (PD‐L1) inhibition sometimes complicates granuloma formation disorders, including sarcoid reaction and exacerbation of tuberculosis 7,8 . SSG formation appears to be a more frequent event than these granuloma‐forming adverse events.…”

Section: Discussionmentioning

confidence: 99%

Identification of characteristic subepithelial surface granulomatosis in immune‐related adverse event‐associated enterocolitis

et al. 2021

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Immune checkpoint inhibitors (ICIs) have provided an additional treatment option for various types of human cancers. However, ICIs often induce various immune‐related adverse events (irAEs). Enterocolitis is a major irAE with poorly understood histopathological characteristics. In this study, we retrospectively investigated the histopathology of colon tissue samples from 17 patients treated with ICIs. There were two major histological patterns of colitis: an ulcerative colitis‐like pattern and a graft vs host disease‐like pattern. Although these two patterns of colitis were mutually exclusive, both patterns often showed a characteristic that we call “subepithelial surface granulomatosis” (SSG), which has not been reported in other types of colitis. SSG was found even in colon tissue without symptoms or endoscopic findings of colitis. Given the increasing reports of sarcoid reaction or exacerbation of tuberculosis after treatment with ICIs, granuloma formation could be a histological hallmark of systemic immune activation by ICIs. Although statistical significance was not obtained, probably because of the small sample size, SSG may be a surrogate biomarker of systemic anticancer immune activation. We propose that a prospective study with larger sample size be performed.

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“…Thoracic metastases are very common in metastatic melanoma. They may appear as lung nodules, which is the most frequent pattern, but also as hilar or mediastinal lymph nodes [ 1 , 3 ]. Therefore, a suspicious thoracic lesion in melanoma patients has a strong possibility to be melanoma recurrence or progression.…”

Section: Discussionmentioning

confidence: 99%

Melanoma and Sarcoidosis in Patients Receiving or Not Antineoplastic Therapy

et al. 2021

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Sarcoidosis and sarcoid-like reactions have been associated with many solid tumors including malignant melanoma. There are reports of melanoma patients who develop sarcoidosis without having received any antineoplastic treatment, but there are also melanoma patients who have received immunotherapy or targeted therapy and, therefore, develop drug-associated sarcoidosis. Herein, we describe 2 cases of thoracic sarcoidosis which occurred in asymptomatic patients with known malignant melanoma. The first patient had metastatic disease, and she was under melanoma treatment with BRAF/MEK inhibitors at the time of sarcoidosis diagnosis. The second case involves a patient with early stage melanoma who had received no antineoplastic treatment. In both cases, the thoracic lesions were suspicious for metastatic involvement, and it was the biopsy which gave the diagnosis of granulomatous disease. Sarcoidosis induced by immune checkpoint or BRAF/MEK inhibitors seems to be more frequent in real-world studies than in large phase 3 melanoma trials. Sarcoidosis can mimic metastasis, predominately in mediastinum, representing a diagnostic pitfall. Therefore, biopsies must always be performed to exclude the metastatic spread before initiation of any antineoplastic treatment.

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Drug-induced sarcoidosis-like reaction in adjuvant immunotherapy: Increased rate and mimicker of metastasis

Cited by 55 publications

References 26 publications

Challenges in sarcoidosis and sarcoid‐like reactions associated to immune checkpoint inhibitors: A narrative review apropos of a case

Challenges in sarcoidosis and sarcoid‐like reactions associated to immune checkpoint inhibitors: A narrative review apropos of a case

Identification of characteristic subepithelial surface granulomatosis in immune‐related adverse event‐associated enterocolitis

Melanoma and Sarcoidosis in Patients Receiving or Not Antineoplastic Therapy

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