Rafaela Kramer1, Anne Zaremba2, Alvaro Moreira3, Selma Ugurel2, Douglas B Johnson4, Jessica C Hassel5, Martin Salzmann5, Anja Gesierich6, Alison Weppler7, Lavinia Spain7, Carmen Loquai8, Milena Dudda8, Claudia Pföhler9, Adriana Hepner10, Georgina V Long11, Alexander M Menzies11, Matteo S Carlino12, Michael M Sachse13, Céleste Lebbé14, Barouyr Baroudjian14, Tomohiro Enokida15, Makoto Tahara15, Max Schlaak16, Kinan Hayani17, Paul J Bröckelmann18, Friedegund Meier19, Lydia Reinhardt19, Philip Friedlander3, Thomas Eigentler20, Katharina C Kähler21, Carola Berking1, Lisa Zimmer2, Lucie Heinzerling22. 1. Department of Dermatology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany; Deutsches Zentrum Immuntherapie (DZI), Erlangen, Germany; Comprehensive Cancer Center Erlangen-European Metropolitan Area of Nürnberg (CCC ER-EMN), Erlangen, Germany. 2. Department of Dermatology, Venerology und Allergology, University Hospital Essen, Essen, Germany. 3. Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai, New York, NY, USA. 4. Vanderbilt University Medical Center, Department of Medicine, Division of Hematology and Oncology, Nashville, USA. 5. Skin Cancer Center, Department of Dermatology and National Center for Tumor Diseases (NCT), University Hospital Heidelberg, Heidelberg, Germany. 6. Department of Dermatology, Venereology and Allergology, University Hospital Würzburg, Würzburg, Germany. 7. Medical Oncology Department, Peter MacCallum Cancer Centre, Melbourne, Australia. 8. Department of Dermatology, University Medical Center, Mainz, Germany. 9. Department of Dermatology, Saarland University Medical Center, Homburg/Saar, Germany. 10. Department of Medical Oncology, Melanoma Institute Australia, Sydney, Australia; Medical Oncology Service, Instituto do Cancer do Estado de Sao Paulo, Sao Paulo, Brazil. 11. Melanoma Institute Australia, University of Sydney, Royal North Shore and Mater Hospitals, Sydney, NSW, Australia. 12. Westmead and Blacktown Hospitals, Melanoma Institute Australia and the University of Sydney, NSW, Australia. 13. Department of Dermatology, Allergology and Phlebology, Bremerhaven Reinkenheide Hospital, Bremerhaven, Germany. 14. APHP, Department of Dermatology, Saint-Louis Hospital, Université de Paris, INSERM U976, Paris, France. 15. Department of Head and Neck Medical Oncology, National Cancer Center Hospital East, Chiba, Japan. 16. Department of Dermatology, Charité University Hospital, Berlin, Germany. 17. Department of Dermatology and Allergy, LMU, University Hospital, Munich, Germany. 18. Department I of Internal Medicine, Centre of Integrated Oncology Aachen Bonn Cologne Duesseldorf (CIO ABCD), Faculty of Medicine and University Hospital of Cologne, University of Cologne, Cologne, Germany. 19. Skin Cancer Center at the University Cancer Centre Dresden and National Center for Tumor Diseases, Dresden, Germany; Department of Dermatology, University Hospital Carl Gustav Carus, TU Dresden, Germany. 20. Department of Dermatology, University Hospital Tübingen, Germany. 21. Department of Dermatology, University Hospital Kiel, Kiel, Germany. 22. Department of Dermatology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany; Deutsches Zentrum Immuntherapie (DZI), Erlangen, Germany; Comprehensive Cancer Center Erlangen-European Metropolitan Area of Nürnberg (CCC ER-EMN), Erlangen, Germany; Department of Dermatology and Allergy, LMU, University Hospital, Munich, Germany. Electronic address: Lucie.Heinzerling@med.uni-muenchen.de.
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 1-128 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.
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 1-128 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.
Authors: Dirk Tomsitz; Max Schlaak; Sarah Zierold; Giulia Pesch; Thomas U Schulz; Genoveva Müller; Christine Zecha; Lars E French; Lucie Heinzerling Journal: Cancers (Basel) Date: 2022-07-05 Impact factor: 6.575
Authors: Anne Zaremba; Rafaela Kramer; Viola De Temple; Stefanie Bertram; Martin Salzmann; Anja Gesierich; Lydia Reinhardt; Barouyr Baroudjian; Michael M Sachse; Gunhild Mechtersheimer; Douglas B Johnson; Alison M Weppler; Lavinia Spain; Carmen Loquai; Milena Dudda; Claudia Pföhler; Adriana Hepner; Georgina V Long; Alexander M Menzies; Matteo S Carlino; Céleste Lebbé; Tomohiro Enokida; Makoto Tahara; Paul J Bröckelmann; Thomas Eigentler; Katharina C Kähler; Ralf Gutzmer; Carola Berking; Selma Ugurel; Nadine Stadtler; Antje Sucker; Jürgen C Becker; Elisabeth Livingstone; Friedegund Meier; Jessica C Hassel; Dirk Schadendorf; Maher Hanoun; Lucie Heinzerling; Lisa Zimmer Journal: Front Oncol Date: 2021-10-21 Impact factor: 6.244
Authors: Tyler C Haddad; Songzhu Zhao; Mingjia Li; Sandip H Patel; Andrew Johns; Madison Grogan; Gabriella Lopez; Abdul Miah; Lai Wei; Gabriel Tinoco; Brian Riesenberg; Zihai Li; Alexa Meara; Erin M Bertino; Kari Kendra; Gregory Otterson; Carolyn J Presley; Dwight H Owen Journal: Cancer Immunol Immunother Date: 2021-10-07 Impact factor: 6.630
Authors: Maria Florencia Tellechea; Flávia S Donaires; Vinícius S de Carvalho; Bárbara A Santana; Fernanda B da Silva; Raissa S Tristão; Lílian F Moreira; Aline F de Souza; Yordanka M Armenteros; Lygia V Pereira; Rodrigo T Calado Journal: Cell Death Dis Date: 2022-04-28 Impact factor: 9.685