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Cancer Immunology, Immunotherapy

, Volume 67, Issue 5, pp 825–834 | Cite as

Ipilimumab in metastatic melanoma patients with pre-existing autoimmune disorders

  • Katharina C. KählerEmail author
  • Thomas K. Eigentler
  • Anja Gesierich
  • Lucie Heinzerling
  • Carmen Loquai
  • Friedegund Meier
  • Frank Meiss
  • Claudia Pföhler
  • Max Schlaak
  • Patrick Terheyden
  • Kai M. Thoms
  • Mirjana Ziemer
  • Lisa Zimmer
  • Ralf Gutzmer
  • For the German Dermatologic Cooperative Oncology Group (DeCOG)
Original Article

Abstract

Background

Ipilimumab and programmed death (PD) 1-antibodies are effective treatment options in metastatic melanoma. The safety and efficacy of ipilimumab in patients with pre-existing autoimmune disorders (AD) has only been evaluated in a selected number of patients.

Methods

We performed a retrospective analysis in 14 German skin cancer centers for patients with metastatic melanoma and pre-existing AD treated with ipilimumab.

Results

41 patients with 44 pre-existing AD were treated with ipilimumab (thyroiditis n = 15, rheumatoid n = 11, dermatologic n = 10, Crohn’s disease/ulcerative colitis n = 3, neurological n = 2, sarcoidosis n = 2, pancreatitis n = 1). 3 out of 41 patients had two AD, 11 patients required immunosuppressants at the time of induction of ipilimumab. 12 patients (29.2%) experienced a flare of their pre-existing AD, mainly patients with rheumatoid or dermatologic diseases. Additional immune-related adverse events (irAEs) occurred in 12 patients (29.2%). In 23 patients (56%) neither a change of their AD nor additional irAEs were observed. Objective responses were seen in five patients (one complete remission, four partial remissions, 12.1%).

Conclusion

This is the largest series of patients with pre-existing AD and treatment with ipilimumab reported. Flares of pre-existing AD were observed but manageable. Response rates and occurrence of new irAEs were comparable to previous trials. Thus, in this patient subgroup, ipilimumab can be a treatment option after a thorough discussion of pros and cons and taking severity and activity of the preexisting AD into account.

Keywords

Ipilimumab Melanoma Immune-related adverse events Autoimmunity 

Abbreviations

AD

Autoimmune disorders

CREST

Syndrome Calcinosis cutis-Raynaud phenomenon-Esophageal Dysmotility-Sclerodactyly-Telangiectasia-syndrome

ECOG

Eastern Cooperative Oncology Group

ICI

Immune checkpoint inhibitor

irAEs

Immune-related adverse events

LETM

Longitudinally extensive transverse myelitis

Notes

Authors’ contributions

Authors whose names appear on this paper have contributed sufficiently to the scientific work, and therefore, share collective responsibility and accountability for the results. Katharina C. Kähler and Ralf Gutzmer planned the project. Katharina C. Kähler, Thomas K. Eigentler, Anja Gesierich, Lucie Heinzerling, Carmen Loquai, Friedegund Meier, Frank Meiss, Claudia Pföhler, Max Schlaak, Patrick Terheyden, Kai M. Thoms, Mirjana Ziemer, Lisa Zimmer, Ralf Gutzmer contributed with the data collection. Katharina C. Kähler, Ralf Gutzmer, Lucie Heinzerling and Mirjana Ziemer contributed to the interpretation of the results. Katharina C. Kähler took the lead in writing the manuscript. All authors provided critical feedback and helped shape the manuscript.

Funding

No funding.

Compliance with ethical standards

Research involving human participants and/or animals

Human participants were involved but only by the retrospective chart review. Ethics approval for the data collection was obtained from the Ethics committee of Hannover Medical School (vote number 1612).

Conflict of interest

Kaehler KC serves as consultant to Roche, Bristol-Myers Squibb (BMS), MSD Sharp& Dohme (MSD) and received travel Grants and speaker fees from Roche, BMS, MSD, GlaxoSmithKline (GSK), Amgen. Eigentler TK has no conflicts of interest. Gesierich A serves as consultant/speaker to Roche, BMS, MSD, Novartis, Amgen, Pfizer and received travel grants from Roche, BMS, MSD, GSK and Novartis. Heinzerling L serves as consultant/speaker to Roche, BMS, MSD, Novartis, Amgen, and received travel grants from Roche, BMS, MSD, Roche, Amgen and Novartis. Loquai C serves as consultant to Roche, BMS, MSD, Novartis, Leo, Pierre Fabre, Amgen, La Roche-Posay and received travel Grants and speaker fees from Roche, BMS, MSD, Novartis, Pierre Fabre, Amgen and La Roche-Posay. Meier F has no conflicts of interest. Meiss F serves as consultant /speaker to Roche, BMS, MSD, Amgen, Novartis, GSK and received travel Grants and speaker fees from Roche, BMS, MSD, GSK, Novartis. Pföhler C serves as a consultant/speaker to Roche, BMS, MSD, Amgen, Novartis, GSK and received travel grants and speaker fees from Roche, BMS, MSD, Amgen, Novartis, GSK. Schlaak M serves as consultant to Novartis, BMS, Roche, MSD and received travel Grants and speaker fees from BMS, MSD, Roche and Amgen. Terheyden P serves as consultant/speaker to Roche, BMS, Amgen, Merck, Novartis and received travel grants from Roche, BMS, Merck. Thoms KM serves as consultant/speaker to Roche, BMS, MSD, Novartis and received travel Grants and speaker fees from Roche, BMS, MSD, Novartis. Ziemer M serves as speaker to Roche, BMS, MSD, Amgen, Novartis and received travel Grants and speaker fees from BMS, Amgen. Zimmer L has served as consultant or/and has received honoraria from Roche, BMS, MSD, GSK, Novartis, Merck, and travel support from MSD, BMS, Amgen and Novartis. Gutzmer R serves as speaker to Roche, BMS, GSK, Novartis, Merck Serono, MSD, Almirall-Hermal, Amgen, Galderma, Janssen, Boehringer Ingelheim and received research grants from Novartis, Pfizer, Johnson&Johnson. He serves as consultant to Roche, BMS, GSK, Novartis, MSD, Almirall-Hermal, LEO, Amgen, Pfizer, Pierre Fabre, La Roche-Posay, Merck Serono and Regeneron.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Katharina C. Kähler
    • 1
    Email author
  • Thomas K. Eigentler
    • 2
  • Anja Gesierich
    • 3
  • Lucie Heinzerling
    • 4
  • Carmen Loquai
    • 5
  • Friedegund Meier
    • 6
  • Frank Meiss
    • 7
  • Claudia Pföhler
    • 8
  • Max Schlaak
    • 9
  • Patrick Terheyden
    • 10
  • Kai M. Thoms
    • 11
  • Mirjana Ziemer
    • 12
  • Lisa Zimmer
    • 13
  • Ralf Gutzmer
    • 14
  • For the German Dermatologic Cooperative Oncology Group (DeCOG)
  1. 1.Department of Dermatology, Campus KielUniversity Hospital Schleswig-Holstein (UKSH)KielGermany
  2. 2.Department of DermatologyEberhard-Karls University of TübingenTübingenGermany
  3. 3.Department of DermatologyUniversity Hospital WürzburgWürzburgGermany
  4. 4.Department of DermatologyUniversity Hospital ErlangenErlangenGermany
  5. 5.Department of DermatologyUniversity Medical Center of MainzMainzGermany
  6. 6.Department of DermatologyUniversity of DresdenDresdenGermany
  7. 7.Department of Dermatology, Medical Center - Faculty of MedicineUniversity of FreiburgFreiburgGermany
  8. 8.Department of DermatologySaarland University Medical SchoolHomburg/saarGermany
  9. 9.Department of Dermatology, Skin Cancer Center at Center of Integrated Oncology (CIO)University Hospital CologneCologne-BonnGermany
  10. 10.Department of DermatologyCampus LübeckUniversity, Hospital (UKSH)LübeckGermany
  11. 11.Department of DermatologyUniversity Medical Center GöttingenGöttingenGermany
  12. 12.Department of DermatologyUniversity Hospital LeipzigLeipzigGermany
  13. 13.Department of Dermatology, Essen, Germany and German Cancer Consortium (DKTK)University Duisburg-Essen, University Hospital EssenHeidelbergGermany
  14. 14.Department of Dermatology and Allergy, Skin Cancer Center HannoverHannover Medical SchoolHanoverGermany

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