Severe hemophagocytic lymphohistiocytosis in a melanoma patient treated with ipilimumab + nivolumab

Journal for Immunotherapy of Cancer
Andrew HantelThomas F Gajewski

Abstract

Treatment of metastatic melanoma patients with immune checkpoint inhibitors is an important standard of care. Side effects are due to immune activation, can affect virtually all organ systems, and are occasionally severe. Although hematologic toxicity has been reported, we present a case of hemophagocytic lymphohistiocytosis (HLH) due to immune checkpoint inhibitor therapy. A patient with metastatic melanoma was treated with one course of ipilimumab + nivolumab and presented 3 weeks later with severe anemia and hyperferritinemia. A bone marrow biopsy revealed necrotic tumor cells, infiltrating T cells, and hemophagocytosis. The patient was treated with high-dose steroids; 12 months later, the patient remains off all therapy and in complete remission of both HLH and metastatic melanoma. The hemophagocytic syndromes are attributable to dysregulated immune activation and share pathophysiologic mechanisms with immune activation from checkpoint inhibitors. Increasing use of regimens that include immune checkpoint inhibition require vigilant monitoring for immune-activating side effects as they can occasionally be life threatening, as in this case of HLH.

References

Nov 1, 1996·Journal of Pediatric Hematology/oncology·R M EgelerA Filipovich
Aug 29, 2006·Pediatric Blood & Cancer·Jan-Inge HenterGritta Janka
Dec 5, 2008·Cancer Immunology, Immunotherapy : CII·Ilyssa O GordonThomas F Gajewski
Jun 8, 2010·The New England Journal of Medicine·F Stephen HodiWalter J Urba
May 18, 2011·The Journal of Clinical Investigation·Edward M BehrensGary A Koretzky
May 25, 2011·Blood·Jennifer E LykensMichael B Jordan
Aug 21, 2013·The Journal of Pediatrics·Shanmuganathan Chandrakasan, Alexandra H Filipovich
Nov 18, 2014·The New England Journal of Medicine·Caroline RobertPaolo A Ascierto
May 21, 2015·American Society of Clinical Oncology Educational Book·Michael A Postow
Jun 2, 2015·The New England Journal of Medicine·James LarkinJedd D Wolchok
Jul 29, 2015·Advances in Cancer Research·Danny N KhalilTaha Merghoub
Nov 13, 2015·American Journal of Clinical Oncology·Elizabeth I Buchbinder, Anupam Desai
Nov 26, 2015·Annals of Oncology : Official Journal of the European Society for Medical Oncology·S KanameishiK Kabashima
Dec 22, 2015·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Audrey Le RoyOlivier Lambotte
Jan 23, 2016·Melanoma Research·Benjamin Y KongMatteo S Carlino
Mar 18, 2016·The New England Journal of Medicine·Ranjit NairSuresh G Nair
Apr 10, 2016·Journal of the National Comprehensive Cancer Network : JNCCN·Daniel G CoitAnita Engh
Jun 17, 2016·The Oncologist·Elisa González-RodríguezUNKNOWN Spanish Group for Cancer Immuno-Biotherapy (GETICA)
Jul 2, 2016·JAMA Oncology·Claire F FriedmanMichael A Postow
Nov 3, 2016·The New England Journal of Medicine·Vassiliki A Boussiotis
Dec 7, 2016·Case Reports in Oncology·Amruth R PallaDonald Doll
Sep 12, 2017·The New England Journal of Medicine·Jedd D WolchokJames Larkin

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Citations

Apr 16, 2020·Expert Opinion on Drug Safety·Anna M Czarnecka, Piotr Rutkowski
Mar 15, 2020·Journal for Immunotherapy of Cancer·Daniel J OlsonThomas F Gajewski
Oct 24, 2019·Current Topics in Medicinal Chemistry·Congcong ZhuQuangang Zhu
Dec 10, 2019·Rheumatology·Noha Abdel-Wahab, Maria E Suarez-Almazor
Feb 7, 2020·Cancers of the Head & Neck·James KalmukJohn Kaczmar
Oct 21, 2020·Cellular & Molecular Immunology·Laura StraussAntonio Sica
Mar 12, 2021·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Rafaela KramerLucie Heinzerling
Sep 2, 2021·Journal of Immunotherapy·Nathaniel R WilsonCristhiam M Rojas-Hernandez
Dec 11, 2021·Hematology·Kelly Walkovich, James A Connelly

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Methods Mentioned

BETA
surgical resection
biopsy

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