Three new cases of bullous pemphigoid during anti‐<scp>PD</scp>‐1 antibody therapy

Naour, S. Le; Peuvrel, L.; Saint‐Jean, M.; Dréno, Brigitte; Quéreux, G.

doi:10.1111/jdv.14579

Cited by 15 publications

(14 citation statements)

References 8 publications

(11 reference statements)

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“…In aggregate, the blocking of PD-1/PD-L1 by nivolumab with IMRT might cause TAMs to abrogate their immunosuppressive function, leading to the development of BP as in our present case. Although several cases of BP developing in anti-PD-1 antibody-treated patients have already been reported [ 18 , 19 , 20 ], in this report, we shed light on the possible pathogenesis of BP developing in a patient treated with nivolumab through M2 macrophages.…”

Section: Discussionmentioning

confidence: 67%

Intensity-Modulated Radiotherapy Triggers Onset of Bullous Pemphigoid in a Patient with Advanced Melanoma Treated with Nivolumab

et al. 2018

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Since the efficacy of ipilimumab on nivolumab-resistant advanced melanoma is extremely low, additional supportive therapy for anti-PD-1 antibody therapy-resistant advanced melanoma is needed. Although several supportive therapies that enhance the antitumor immune response of anti-PD-1 antibodies have already been reported, unexpected immune-related adverse events were detected at the same time. In this report, we describe a patient with advanced melanoma treated with nivolumab followed by intensity-modulated radiotherapy, which might have triggered bullous pemphigoid (BP). Although several cases of BP developing in anti-PD-1 antibody-treated patients have already been reported, in this report, we shed light on the possible pathogenesis of BP developing in a patient treated with nivolumab through M2 macrophages.

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Section: Discussionmentioning

confidence: 67%

Intensity-Modulated Radiotherapy Triggers Onset of Bullous Pemphigoid in a Patient with Advanced Melanoma Treated with Nivolumab

et al. 2018

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“… 79 Bullous pemphigoid, an autoimmune bullous mucocutaneous disease, induced after initiation of immunotherapy has also been reported. 85 To clarify further, a diagnosis of SJS/TEN, DIF or IIF can help eliminate the possibility of autoimmune bullous diseases.…”

Section: Stevens-johnson Syndrome/toxic Epidermal Necrolysismentioning

confidence: 99%

Severe cutaneous adverse reactions induced by targeted anticancer therapies and immunotherapies

Chen¹,

Wu²,

Ng³

et al. 2018

CMAR

123

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With the increasing use of targeted anticancer drugs and immunotherapies, there have been a substantial number of reports concerning life-threatening severe cutaneous adverse reactions (SCARs), including Stevens–Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug rash with eosinophilia and systemic symptoms, drug-induced hypersensitivity syndrome, and acute generalized exanthematous pustulosis. Although the potential risks and characteristics for targeted anticancer agent- and immunotherapy-induced SCAR were not well understood, these serious adverse reactions usually result in morbidity and sequela. As a treatment guideline for this devastating condition is still unavailable, prompt withdrawal of causative drugs is believed to be a priority of patient management. In this review, we outline distinct types of SCARs caused by targeted anticancer therapies and immunotherapies. Also, we discuss the clinical course, latency, concomitant medication, tolerability of rechallenge or alternatives, tumor response, and mortality associated with these devastating conditions. Imatinib, vemurafenib, and rituximab were the top three offending medications that most commonly caused SJS/TEN, while EGFR inhibitors were the group of drugs that most frequently induced SJS/TEN. For drug rash with eosinophilia and systemic symptoms/drug-induced hypersensitivity syndrome and acute generalized exanthematous pustulosis, imatinib was also the most common offending drug. Additionally, we delineated 10 SCAR cases related to innovative immunotherapies, including PD1 and CTLA4 inhibitors. There was a wide range of latency periods: 5.5–91 days (median). Only eight of 16 reported patients with SCAR showed clinical responses. Targeted anticancer drugs and immunotherapies can lead to lethal SCAR (14 deceased patients were identified as suffering from SJS/TEN). The mortality rate of TEN was high: up to 52.4%. The information compiled herein will serve as a solid foundation to formulate ideas for early recognition of SCAR and to discontinue offending drugs for better management.

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“…We examined the intrinsic accountability of pembrolizumab therapy on MMP induction in our patient with metastatic melanoma because of its extrinsic accountability based on the following reports: (i) MMP and BP have immunological similarities ( 7 ); (ii) intrinsic accountability of anti PD-1/PD-L1 treatments on BP induction: 27 BP have been reported as case reports or short series ( 32 – 49 ) and two BPs listed as adverse drug reaction in two large trials with anti PD-1 ( 50 , 51 ); (iii) recently, one pembrolizumab-associated MMP case report ( 52 ), and (iv) some of the anti PD-1/PD-L1-associated BPs had atypical clinical phenotypes ( 33 – 35 , 42 , 47 ).…”

Section: Discussionmentioning

confidence: 99%

“…Recently, between 2015 and 2018, 18 case reports or small series described 27 patients who developed BP while receiving anti PD-1/PD-L1 therapy, including three with negative DIF ( 35 , 37 ) or without DIF confirmation ( 47 ) but with typical clinical presentations (Tables 1 , 2 ). Fourteen patients received anti PD-1 nivolumab therapy (patients 2, 4, 7, 9, 10, 13, 15, 18, 20, 22, 23, and 25–27) ( 33 , 35 , 38 , 42 , 44 , 46 , 47 , 49 ), 11 received anti PD-1 pembrolizumab therapy (patients 1, 5, 6, 8, 11, 12, 14,16, 19, 21, and 24) ( 32 , 34 – 37 , 39 , 40 , 43 , 45 , 48 ), one received anti-PD-L1 durvalumab therapy (patient 3) ( 33 ), and one received anti-PD-L1 atezolizumab therapy (patient 17) ( 41 ). Six of the 27 patients received ipilimumab therapy before anti PD-1, one received an association of ipilimumab and nivolumab therapy, and one received ipilimumab therapy after treatment with nivolumab.…”

Section: Discussionmentioning

confidence: 99%

Mucous Membrane Pemphigoid, Bullous Pemphigoid, and Anti-programmed Death-1/ Programmed Death-Ligand 1: A Case Report of an Elderly Woman With Mucous Membrane Pemphigoid Developing After Pembrolizumab Therapy for Metastatic Melanoma and Review of the Literature

et al. 2018

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An 83-year-old patient developed erosions and a blister of the gingival mucous membrane, 6 months after discontinuation of the anti-programmed death-1 (anti PD-1) pembrolizumab therapy administered for 10 months for a metastatic melanoma. A diagnosis of mild mucous membrane pemphigoid (MMP) was made. Complete remission of MMP was rapidly obtained with minimal therapy (doxycycline). MMP remained in complete remission after a 3-month follow-up since discontinuation of the doxycycline therapy and no evidence of relapse of the melanoma was observed after a 14-month follow-up since discontinuation of the pembrolizumab therapy. The widespread use of anti PD-1 and anti-programmed death-ligand-1 (PD-L1) in several malignancies reveals new adverse events. MMP describes a group of chronic, inflammatory, mucous membrane-predominant, subepithelial auto-immune blistering diseases. It is clinically distinct from bullous pemphigoid another autoimmune blistering disease but shares some immunological similarities with it. Twenty-nine cases of bullous pemphigoid associated with anti PD-1/PD-L1 have been reported in the literature and one of MMP. Here, we described the case of a MMP developed after pembrolizumab and discussed the accountability of anti PD-1/PD-L1 in our case and the previous reported bullous pemphigoid and MMP cases using the Begaud system scoring.

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Three new cases of bullous pemphigoid during anti‐PD‐1 antibody therapy

Cited by 15 publications

References 8 publications

Intensity-Modulated Radiotherapy Triggers Onset of Bullous Pemphigoid in a Patient with Advanced Melanoma Treated with Nivolumab

Intensity-Modulated Radiotherapy Triggers Onset of Bullous Pemphigoid in a Patient with Advanced Melanoma Treated with Nivolumab

Severe cutaneous adverse reactions induced by targeted anticancer therapies and immunotherapies

Mucous Membrane Pemphigoid, Bullous Pemphigoid, and Anti-programmed Death-1/ Programmed Death-Ligand 1: A Case Report of an Elderly Woman With Mucous Membrane Pemphigoid Developing After Pembrolizumab Therapy for Metastatic Melanoma and Review of the Literature

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