Haemophagocytic lymphohistiocytosis following the anti-PD-1 nivolumab in a patient with gastric cancer and ankylosing spondylitis
  • Clara Long
    Department of Medicine, McGill University Health Centre, Montreal, Canada
  • Abdulrahman Al-Abdulmalek
    Department of Medicine, McGill University Health Centre, Montreal, Canada
  • Jonathan Lai
    Department of Pathology, McGill University Health Centre, Montreal, Canada
  • David G. Haegert
    Department of Pathology, McGill University Health Centre, Montreal, Canada
  • Stephane Isnard
    Research Institute of the McGill University Health Centre, Montreal, Canada; Chronic Viral Illness Service, McGill University Health Centre, Montreal, Canada
  • Denis Cournoyer
    Department of Medicine, McGill University Health Centre, Montreal, Canada; Department of Medicine and Oncology, McGill University, Montreal, Canada
  • Jean-Pierre Routy
    Department of Medicine, McGill University Health Centre, Montreal, Canada; Research Institute of the McGill University Health Centre, Montreal, Canada

Keywords

Hemophagocytic lymphohistiocytosis, immunotherapy, anti-PD1, gastric cancer, ankylosing spondylitis

Abstract

Background: Autoimmune diseases are not contraindications for immune checkpoint inhibitors (ICI) therapy in patients with cancer. However, immune-related adverse events (irAEs) are frequently observed in patients receiving ICIs including dermatitis, thyroiditis, colitis, and pneumonitis. Thrombocytopenic purpura, aplasia, and haemophagocytic lymphohistiocytosis (HLH) are rarely observed during ICIs.
Case description: We report the case of a male patient with pre-existing untreated HLA B27 and ankylosing spondylitis with gastric cancer and liver metastases. The 79-year-old man was treated with anti-HER2 trastuzumab and anti-PD-1 nivolumab. Seventeen days after the seventh cycle of treatment, he presented at the emergency department with acute fever, confusion, and hypotension. Laboratory results showed pancytopenia, and elevation of ferritin and triglyceride. No infections were detected. Although not seen in a bone marrow biopsy, clinical presentation, and absence of infection, together with an H-score of 263, indicated HLH. The patient was treated with dexamethasone for four days and discharged on a tapering dose of steroids. At the two-month follow-up, clinical presentation was normal and blood test almost normalised. At 8 months, no liver metastases were observed.
Conclusions: In a patient with a pre-existing autoimmune condition, immunotherapy led to the development of HLH, which was controlled by glucocorticoid. Absence of the feature of haemophagocytosis in the bone marrow biopsy did not exclude the diagnosis, as HLH can occur in the spleen or in the liver. Glucocorticoid therapy did not prevent the anti-cancer effect of ICIs, and liver metastases disappeared 8 months post-HLH. This case warrants further research on the interplay between autoimmunity and ICI response, as well as ICI-induced irAEs.

VIEW THE ENTIRE ARTICLE

References

  • Esfahani K, Elkrief A, Calabrese C, Lapointe R, Hudson M, Routy B, et al. Moving towards personalized treatments of immune-related adverse events. Nat Rev Clin Oncol 2020;17:504–515.
  • Fardet L, Galicier L, Lambotte O, Marzac C, Aumont C, Chahwan D, et al. Development and validation of the HScore, a score for the diagnosis of reactive hemophagocytic syndrome. Arthritis Rheumatol 2014;66:2613–2620.
  • Wiseman D, Lin J, Routy J-P, Samoukovic G. Haemophagocytic lymphohistiocytosis in an adult with postacute COVID-19 syndrome. BMJ Case Rep 2021;14:e245031.
  • Soy M, Atagündüz P, Atagündüz I, Sucak GT. Hemophagocytic lymphohistiocytosis: a review inspired by the COVID-19 pandemic. Rheumatol Int 2021;41:7–18.
  • Les I, Martínez M, Pérez-Francisco I, Cabero M, Teijeira L, Arrazubi V, et al. Predictive biomarkers for checkpoint inhibitor immune-related adverse events. Cancers (Basel) 2023;15:1629.
  • Wei Y, He W, Sun W, Wu C, Ren D, Wang X, et al. Hemophagocytic lymphohistiocytosis in two patients following treatment with pembrolizumab: two case reports and a literature review. Transl Cancer Res 2022;11:2960–2966.
  • Abdel-Wahab N, Shah M, Lopez-Olivo MA, Suarez-Almazor ME. Use of immune checkpoint inhibitors in the treatment of patients with cancer and preexisting autoimmune disease: a systematic review. Ann Intern Med 2018;168:121–130.
  • Ibis B, Aliazis K, Cao C, Yenyuwadee S, Boussiotis VA. Immune-related adverse effects of checkpoint immunotherapy and implications for the treatment of patients with cancer and autoimmune diseases. Front Immunol 2023;14:1197364.
  • La Marle S, Richard-Colmant G, Fauvernier M, Ghesquières H, Hot A, Sève P, et al. Mortality and associated causes in hemophagocytic lymphohistiocytosis: a multiple-cause-of-death analysis in France. J Clin Med 2023;12:1696.
  • Buchanan WW, Kean CA, Rainsford KD, Kean WF. Spondyloarthropathies and arthritis post-infection: a historical perspective. Inflammopharmacology 2024;32:73–81.
  • Epistola R, Chao J, Lee J. Evolving landscape of targeted treatment options for HER2-positive gastric/gastroesophageal adenocarcinomas. Clin Adv Hematol Oncol 2023;21:312–320.
  • Park JH, Seo YM, Han SB, Kim KH, Rhim JW, Chung NG, et al. Recurrent macrophage activation syndrome since toddler age in an adolescent boy with HLA B27 positive juvenile ankylosing spondylitis. Korean J Pediatr 2016;59:421–424.
  • Chang H, Shin Y-W, Keam B, Kim M, Im S-A, Lee S-T. HLA-B27 association of autoimmune encephalitis induced by PD-L1 inhibitor. Ann Clin Transl Neurol 2020;7:2243–2250.
  • Trautmann L, Janbazian L, Chomont N, Said EA, Gimmig S, Bessette B, et al. Upregulation of PD-1 expression on HIV-specific CD8+ T cells leads to reversible immune dysfunction. Nat Med 2006;12:1198–1202.
  • Singh N, Hocking AM, Buckner JH. Immune-related adverse events after immune check point inhibitors: understanding the intersection with autoimmunity. Immunol Rev 2023;318:81–88.
  • Jiang N, Yu Y, Zhang M, Tang Y, Wu D, Wang S, et al. Association between germ-line HLA and immune-related adverse events. Front Immunol 2022;13:952099.
  • Laderian B, Koehn K, Holman C, Lyckholm L, Furqan M. Association of hemophagocytic lymphohistiocytosis and programmed death 1 checkpoint inhibitors. J Thorac Oncol 2019;14:e77–78.
  • Views: 94
    HTML downloads: 12
    PDF downloads: 59


    Published: 2024-03-28
    Issue: 2024: LATEST ONLINE (view)


    How to cite:
    1.
    Long C, Al-Abdulmalek A, Lai J, Haegert DG, Isnard S, Cournoyer D, Routy J-P. Haemophagocytic lymphohistiocytosis following the anti-PD-1 nivolumab in a patient with gastric cancer and ankylosing spondylitis. EJCRIM 2024;11 doi:10.12890/2024_004370.