Top

Investigational New Drugs

Published in:

29-09-2023 | Bullous Pemphigoid | Research

Clinical characterization, treatment, and outcome of nivolumab-induced bullous pemphigoid

Authors: Miao Liu, Maoye Yuan, Wei Sun, Zuojun Li, Xingchen Zhou, Chunjiang Wang

Published in: Investigational New Drugs | Issue 6/2023

Abstract

Background

Bullous pemphigoid (BP) is a serious and rare complication of nivolumab. This study aimed to explore the clinical characteristics of nivolumab-induced BP and provide a reference for prevention and treatment of BP.

Methods

Literature on nivolumab-induced BP was collected for retrospective analysis by searching both Chinese and English databases as of July 31, 2023.

Results

Sixty patients were included, with a median age of 71 years (range 30 to 85 years), and they were predominantly male (78.3%). The median time to onset of BP was 31 weeks (range 2.4, 216) after nivolumab administration. Tense bullae (93.3%), pruritus (55.0%), and urticarial plaques (31.7%) were the most common manifestations. Lesions were found on the limbs (50.0%), trunk (38.3%), palms and soles (15.0%). Skin biopsies mainly showed subepidermal bullous/blister (50.0%) and eosinophilic infiltration (46.7%). Direct immunofluorescence showed mainly linear deposition of C3 and IgG (46.7%) at the dermal-epidermal junction. The patients stopped taking nivolumab and received systemic steroids (73.3%), topical steroids (63.3%), monoclonal antibodies (21.7%), doxycycline/minocycline (30.0%) and other treatments. Symptoms improved or were relieved in 88.4% of patients but did not improve in 8.3% of patients.

Conclusion

Clinicians should closely monitor symptoms of BP in those receiving and discontinuing nivolumab, especially in older men. Early diagnosis and timely initiation of treatment may improve patient outcomes.

Gotera N, Weilg P, Heleno C, Ferrari-Gabilondo N (2022) A case of Bullous Pemphigoid Associated with Nivolumab Therapy. Cureus 14(5):e24804. https://doi.org/10.7759/cureus.24804CrossRefPubMedPubMedCentral

Lopez AT, Khanna T, Antonov N, Audrey-Bayan C, Geskin L (2018) A review of bullous pemphigoid associated with PD-1 and PD-L1 inhibitors. Int J Dermatol 57(6):664–669. https://doi.org/10.1111/ijd.13984CrossRefPubMed

Schmidt E, della Torre R, Borradori L (2011) Clinical features and practical diagnosis of bullous pemphigoid. Dermatol Clin. 29(3):427–38, viii-ix. https://doi.org/10.1016/j.det.2011.03.010

Wongvibulsin S, Pahalyants V, Kalinich M et al (2022) Epidemiology and risk factors for the development of cutaneous toxicities in patients treated with immune-checkpoint inhibitors: a United States population-level analysis. J Am Acad Dermatol 86(3):563–572. https://doi.org/10.1016/j.jaad.2021.03.0947CrossRefPubMed

Siegel J, Totonchy M, Damsky W, Berk-Krauss J, Castiglione F Jr, Sznol M et al (2018) Bullous disorders associated with anti-PD-1 and anti-PD-L1 therapy: a retrospective analysis evaluating the clinical and histopathologic features, frequency, and impact on cancer therapy. J Am Acad Dermatol 79(6):1081–1088. https://doi.org/10.1016/j.jaad.2018.07.008CrossRefPubMed

Miyamoto D, Santi CG, Aoki V, Maruta CW (2019) Bullous pemphigoid. An Bras Dermatol 94(2):133–146. https://doi.org/10.1590/abd1806-4841.20199007CrossRefPubMedPubMedCentral

Mazumder A, Darji K, Smith K, Guo M (2022) Two rare cases of bullous pemphigoid associated with immune checkpoint inhibitors. BMJ Case Rep 15(12):e253059. https://doi.org/10.1136/bcr-2022-253059CrossRefPubMed

Hanley T, Papa S, Saha M (2018) Bullous pemphigoid associated with ipilimumab therapy for advanced metastatic melanoma. JRSM Open 9(10):2054270418793029. https://doi.org/10.1177/2054270418793029CrossRefPubMedPubMedCentral

Cuenca-Barrales C, Espadafor-López B, Martínez-López A, Cancela-Díez B, Ruiz-Villaverde R (2019) Bullous pemphigoid in a patient treated with nivolumab. Dermatol Ther 32(5):e13030. https://doi.org/10.1111/dth.13030CrossRefPubMed

10.

Hurkmans DP, Basak EA, van Dijk T, Mercieca D, Schreurs MWJ, Wijkhuijs AJM et al (2019) A prospective cohort study on the pharmacokinetics of nivolumab in metastatic non-small cell lung cancer, melanoma, and renal cell cancer patients. J Immunother Cancer 7(1):192. https://doi.org/10.1186/s40425-019-0669-yCrossRefPubMedPubMedCentral

11.

Delgado JC, Turbay D, Yunis EJ, Yunis JJ, Morton ED, Bhol K, Norman R, Alper CA, Good RA, Ahmed R (1996) A common major histocompatibility complex class II allele HLA-DQB1* 0301 is present in clinical variants of pemphigoid. Proc Natl Acad Sci U S A 93(16):8569–8571. https://doi.org/10.1073/pnas.93.16.8569CrossRefPubMedPubMedCentral

12.

Amber KT, Zikry J, Hertl M (2017) A multi-hit hypothesis of bullous pemphigoid and associated neurological disease: is HLA-DQB1*03:01, a potential link between immune privileged antigen exposure and epitope spreading? HLA 89(3):127–134. https://doi.org/10.1111/tan.12960CrossRefPubMed

13.

Di Lernia V, Casanova DM, Goldust M, Ricci C (2020) Pemphigus Vulgaris and Bullous Pemphigoid: update on diagnosis and treatment. Dermatol Pract Concept 10(3):e2020050. https://doi.org/10.5826/dpc.1003a50CrossRefPubMedPubMedCentral

14.

Moriuchi R, Nishie W, Ujiie H, Natsuga K, Shimizu H (2015) In vivo analysis of IgE autoantibodies in bullous pemphigoid: a study of 100 cases. J Dermatol Sci 78(1):21–25. https://doi.org/10.1016/j.jdermsci.2015.01.013CrossRefPubMed

15.

Boch K, Hammers CM, Goletz S, Kamaguchi M, Ludwig RJ, Schneider SW, Zillikens D, Hadaschik E, Schmidt E Immunoglobulin M pemphigoid. J Am Acad Dermatol. 202;85(6):1486–1492. https://doi.org/10.1016/j.jaad.2021.01.017

16.

Schmidt E, Obe K, Bröcker EB, Zillikens D (2000) Serum levels of autoantibodies to BP180 correlate with disease activity in patients with bullous pemphigoid. Arch Dermatol 136(2):174–178. https://doi.org/10.1001/archderm.136.2.174CrossRefPubMed

17.

Krenacs T, Kiszner G, Stelkovics E, Balla P, Teleki I, Nemeth I et al (2012) Collagen XVII is expressed in malignant but not in benign melanocytic tumors and it can mediate antibody induced melanoma apoptosis. Histochem Cell Biol 138(4):653–667. https://doi.org/10.1007/s00418-012-0981-9CrossRefPubMed

18.

Ellis SR, Vierra AT, Millsop JW, Lacouture ME, Kiuru M (2020) Dermatologic toxicities to immune checkpoint inhibitor therapy: a review of histopathologic features. J Am Acad Dermatol 83(4):1130–1143. https://doi.org/10.1016/j.jaad.2020.04.105CrossRefPubMedPubMedCentral

19.

Wojnarowska F, Kirtschig G, Highet AS, Venning VA, Khumalo NP (2002) British Association of Dermatologists. Guidelines for the management of bullous pemphigoid. Br J Dermatol 147(2):214–221. https://doi.org/10.1046/j.1365-2133.2002.04835.xCrossRefPubMed

20.

Kárpáti H, Marinovic S, Mimouni B, Uzun D, Yayli S, Hertl S, Borradori M (2015) Management of bullous pemphigoid: the european Dermatology Forum consensus in collaboration with the European Academy of Dermatology and Venereology. Br J Dermatol 172(4):867–877. https://doi.org/10.1111/bjd.13717CrossRefPubMed

21.

Munera-Campos M, Plana-Pla A, Rivera N, Boada A, Ferrándiz C (2020) Nivolumab-Induced Bullous Pemphigoid Managed without Drug Withdrawal. Indian J Dermatol 65(3):214–216. https://doi.org/10.4103/ijd.IJD_321_18CrossRefPubMedPubMedCentral

22.

Povilaityte E, Gellrich FF, Beissert S, Abraham S, Meier F, Günther C (2021) Treatment-resistant bullous pemphigoid developing during therapy with immune checkpoint inhibitors. J Eur Acad Dermatol Venereol 35(9):e591–e593. https://doi.org/10.1111/jdv.17321CrossRefPubMed

Title: Clinical characterization, treatment, and outcome of nivolumab-induced bullous pemphigoid
Authors: Miao Liu
Maoye Yuan
Wei Sun
Zuojun Li
Xingchen Zhou
Chunjiang Wang
Publication date: 29-09-2023
Publisher: Springer US
Keywords: Bullous Pemphigoid
Melanoma
Melanoma
Published in: Investigational New Drugs / Issue 6/2023
Print ISSN: 0167-6997
Electronic ISSN: 1573-0646
DOI: https://doi.org/10.1007/s10637-023-01397-w

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 6/2023

Therapeutic effectiveness of anlotinib combined with etoposide in extensive-stage small-cell lung cancer: a single-arm, phase II trial

Pharmacokinetics, pharmacodynamics and efficacy of pemigatinib (a selective inhibitor of fibroblast growth factor receptor 1–3) monotherapy in Chinese patients with advanced solid tumors: a phase i clinical trial

Antitumor activity of the new tyrphostin briva against BRAFV600E-mutant colorectal carcinoma cells

Optimal first-line treatment strategies of systemic therapy for unresectable gastrointestinal neuroendocrine tumors based on the opinions of Japanese experts.

Phase 1/1b open-label, dose-escalation study of fruquintinib in patients with advanced solid tumors in the United States

Clinical characteristics and prognostic impact of immune checkpoint inhibitor-associated myocarditis in advanced non-small cell lung cancer

Keynote webinar | Spotlight on antibody–drug conjugates in cancer