Kramer, Rafaela ORCID: 0000-0002-3967-5289, Zaremba, Anne, Moreira, Alvaro, Ugurel, Selma, Johnson, Douglas B., Hassel, Jessica C., Salzmann, Martin, Gesierich, Anja, Weppler, Alison ORCID: 0000-0003-3769-490X, Spain, Lavinia, Loquai, Carmen, Dudda, Milena, Pfoehler, Claudia, Hepner, Adriana ORCID: 0000-0002-8716-9401, Long, Georgina, V, Menzies, Alexander M., Carlino, Matteo S., Sachse, Michael M., Lebbe, Celeste, Baroudjian, Barouyr, Enokida, Tomohiro, Tahara, Makoto, Schlaak, Max, Hayani, Kinan, Broeckelmann, Paul J., Meier, Friedegund, Reinhardt, Lydia, Friedlander, Philip, Eigentler, Thomas, Kaehler, Katharina C., Berking, Carola, Zimmer, Lisa ORCID: 0000-0002-3680-3521 and Heinzerling, Lucie (2021). Hematological immune related adverse events after treatment with immune checkpoint inhibitors. Eur. J. Cancer, 147. S. 170 - 182. OXFORD: ELSEVIER SCI LTD. ISSN 1879-0852

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Abstract

Introduction: With the increasing use of checkpoint inhibitors, rare immune-related adverse events (irAE) are being identified. Haematological irAE (hem-irAE) are difficult to treat and have shown high mortality rates. In order to improve side-effect management for these potentially life-threatening events, we analysed frequency, severity and outcomes. Patients and methods: Patients who developed hem-irAE while being treated with immune checkpoint inhibitors (ICI) therapy were retrospectively identified from 18 international cancer centres. Results: In total, more than 7626 patients treated with ICI were screened, and 50 patients with hem-irAE identified. The calculated incidence amounts to 0.6% and median onset was 6 weeks after the ICI initiation (range 1e128 weeks). Thrombocytopenia and leucopaenia were the most frequent hem-irAE with 34% (17/50) and 34% (17/50), respectively, followed by anaemia 28% (14/50), hemophagocytic lymphohistiocytosis (4% (2/50)), aplastic anaemia (2% (1/50)), acquired haemophilia A (2% (1/50)) and coagulation deficiency (2% (1/50)). Simultaneous thrombocytopenia and neutropenia occurred in two patients, concurrent anaemia and thrombocytopenia in one patient. Other than cessation of ICI (in 60%) and corticosteroids (in 78%), treatment included second-line immunosuppression in 24% of cases. Events resolved in 78% (39/50), while 18% (9/50) had persistent changes, and 2% (1/50) had fatal outcomes (agranulocytosis). Conclusion: Hem-irAE can affect all haematopoietic blood cell lineages and may persist or even be fatal. Management may require immunosuppression beyond corticosteroids. Although these irAE are rare, treating physicians should be aware, monitor blood counts regularly and promptly act upon detection. (C) 2021 Elsevier Ltd. All rights reserved.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Kramer, RafaelaUNSPECIFIEDorcid.org/0000-0002-3967-5289UNSPECIFIED
Zaremba, AnneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Moreira, AlvaroUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ugurel, SelmaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Johnson, Douglas B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hassel, Jessica C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Salzmann, MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gesierich, AnjaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Weppler, AlisonUNSPECIFIEDorcid.org/0000-0003-3769-490XUNSPECIFIED
Spain, LaviniaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Loquai, CarmenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dudda, MilenaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pfoehler, ClaudiaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hepner, AdrianaUNSPECIFIEDorcid.org/0000-0002-8716-9401UNSPECIFIED
Long, Georgina, VUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Menzies, Alexander M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Carlino, Matteo S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sachse, Michael M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lebbe, CelesteUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Baroudjian, BarouyrUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Enokida, TomohiroUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tahara, MakotoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schlaak, MaxUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hayani, KinanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Broeckelmann, Paul J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Meier, FriedegundUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Reinhardt, LydiaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Friedlander, PhilipUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Eigentler, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kaehler, Katharina C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Berking, CarolaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zimmer, LisaUNSPECIFIEDorcid.org/0000-0002-3680-3521UNSPECIFIED
Heinzerling, LucieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-606935
DOI: 10.1016/j.ejca.2021.01.013
Journal or Publication Title: Eur. J. Cancer
Volume: 147
Page Range: S. 170 - 182
Date: 2021
Publisher: ELSEVIER SCI LTD
Place of Publication: OXFORD
ISSN: 1879-0852
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
OncologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/60693

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