Hemophagocytic Lymphohistiocytosis in a Patient with Rheumatoid Arthritis on Pembrolizumab for Lung Adenocarcinoma

Overview

Journal Intern Med

Specialty General Medicine

Date 2020 Feb 4

PMID 32009093

Citations 13

Authors

Yu Akagi

Nobuyasu Awano

Minoru Inomata

Naoyuki Kuse

Mari Tone

Hanako Yoshimura

Tatsunori Jo

Kohei Takada

Toshio Kumasaka

Takehiro Izumo

Affiliations

Soon will be listed here.

Abstract

Immune checkpoint inhibitors have changed the landscape of classic cancer treatment. However, their use is associated with the emergence of new adverse events. An elderly man with rheumatoid arthritis was started on pembrolizumab for newly diagnosed advanced lung cancer. He subsequently developed hemophagocytic lymphohistiocytosis (HLH), which is potentially fatal but has not been properly established as an immune checkpoint inhibition-induced event. We herein report the case of a patient with pembrolizumab-induced HLH.

Citing Articles

Hemophagocytic lymphohistiocytosis/cytokine release syndrome secondary to neoadjuvant pembrolizumab for triple-negative breast cancer: a case study.

Patton L, Monteith B, Heffernan P, Herzinger T, Wilson B Front Oncol. 2024; 14:1394543.

PMID: 38919527 PMC: 11196757. DOI: 10.3389/fonc.2024.1394543.

A Case Report of Hemophagocytic Lymphohistiocytosis and Meningitis Due to Atezolizumab Treatment for Lung Adenocarcinoma.

Ota H, Munechika M, Tobino K, Uchida K, Muarakami Y Cureus. 2024; 16(4):e58253.

PMID: 38745801 PMC: 11091938. DOI: 10.7759/cureus.58253.

Rheumatic adverse events of immune checkpoint inhibitors in cancer immunotherapy.

Abdel-Wahab N, Suarez-Almazor M Expert Rev Clin Immunol. 2024; 20(8):873-893.

PMID: 38400840 PMC: 11449381. DOI: 10.1080/1744666X.2024.2323966.

Hemophagocytic lymphohistiocytosis following pembrolizumab and bevacizumab combination therapy for cervical cancer: a case report and systematic review.

Zhai C, Jin X, You L, Yan N, Dong J, Qiao S BMC Geriatr. 2024; 24(1):32.

PMID: 38191289 PMC: 10773023. DOI: 10.1186/s12877-023-04625-3.

Systemic inflammatory syndromes as life-threatening side effects of immune checkpoint inhibitors: case report and systematic review of the literature.

Liu L, Skribek M, Harmenberg U, Gerling M J Immunother Cancer. 2023; 11(3).

PMID: 36878533 PMC: 9990684. DOI: 10.1136/jitc-2022-005841.

References

Wang H, Xiong L, Tang W, Zhou Y, Li F . A systematic review of malignancy-associated hemophagocytic lymphohistiocytosis that needs more attentions. Oncotarget. 2017; 8(35):59977-59985. PMC: 5601794. DOI: 10.18632/oncotarget.19230. View

Cho J, Kim J, Lee J, Kim Y, Kim S, Lee Y . Characteristics, incidence, and risk factors of immune checkpoint inhibitor-related pneumonitis in patients with non-small cell lung cancer. Lung Cancer. 2018; 125:150-156. DOI: 10.1016/j.lungcan.2018.09.015. View

Golden M, Katz R, Balk R, Golden H . The relationship of preexisting lung disease to the development of methotrexate pneumonitis in patients with rheumatoid arthritis. J Rheumatol. 1995; 22(6):1043-7. View

Zhang K, Jordan M, Marsh R, Johnson J, Kissell D, Meller J . Hypomorphic mutations in PRF1, MUNC13-4, and STXBP2 are associated with adult-onset familial HLH. Blood. 2011; 118(22):5794-8. PMC: 3228496. DOI: 10.1182/blood-2011-07-370148. View

Johnson D, Balko J, Compton M, Chalkias S, Gorham J, Xu Y . Fulminant Myocarditis with Combination Immune Checkpoint Blockade. N Engl J Med. 2016; 375(18):1749-1755. PMC: 5247797. DOI: 10.1056/NEJMoa1609214. View

Johnson D, Sullivan R, Ott P, Carlino M, Khushalani N, Ye F . Ipilimumab Therapy in Patients With Advanced Melanoma and Preexisting Autoimmune Disorders. JAMA Oncol. 2015; 2(2):234-40. DOI: 10.1001/jamaoncol.2015.4368. View

Menzies A, Johnson D, Ramanujam S, Atkinson V, Wong A, Park J . Anti-PD-1 therapy in patients with advanced melanoma and preexisting autoimmune disorders or major toxicity with ipilimumab. Ann Oncol. 2016; 28(2):368-376. DOI: 10.1093/annonc/mdw443. View

Abdel-Wahab N, Shah M, Lopez-Olivo M, Suarez-Almazor M . Use of Immune Checkpoint Inhibitors in the Treatment of Patients With Cancer and Preexisting Autoimmune Disease: A Systematic Review. Ann Intern Med. 2018; 168(2):121-130. DOI: 10.7326/M17-2073. View

Jordan M, Allen C, Weitzman S, Filipovich A, McClain K . How I treat hemophagocytic lymphohistiocytosis. Blood. 2011; 118(15):4041-52. PMC: 3204727. DOI: 10.1182/blood-2011-03-278127. View

10.

Trottestam H, Horne A, Arico M, Egeler R, Filipovich A, Gadner H . Chemoimmunotherapy for hemophagocytic lymphohistiocytosis: long-term results of the HLH-94 treatment protocol. Blood. 2011; 118(17):4577-84. PMC: 3208276. DOI: 10.1182/blood-2011-06-356261. View

11.

Shah D, Shrestha R, Ramlal R, Hatton J, Saeed H . Pembrolizumab associated hemophagocytic lymphohistiocytosis. Ann Oncol. 2017; 28(6):1403. DOI: 10.1093/annonc/mdx113. View

12.

Haratani K, Hayashi H, Chiba Y, Kudo K, Yonesaka K, Kato R . Association of Immune-Related Adverse Events With Nivolumab Efficacy in Non-Small-Cell Lung Cancer. JAMA Oncol. 2017; 4(3):374-378. PMC: 6583041. DOI: 10.1001/jamaoncol.2017.2925. View

13.

Gordon S, Maute R, Dulken B, Hutter G, George B, McCracken M . PD-1 expression by tumour-associated macrophages inhibits phagocytosis and tumour immunity. Nature. 2017; 545(7655):495-499. PMC: 5931375. DOI: 10.1038/nature22396. View

14.

Alarcon G, Kremer J, Macaluso M, Weinblatt M, Cannon G, Palmer W . Risk factors for methotrexate-induced lung injury in patients with rheumatoid arthritis. A multicenter, case-control study. Methotrexate-Lung Study Group. Ann Intern Med. 1997; 127(5):356-64. DOI: 10.7326/0003-4819-127-5-199709010-00003. View

15.

Hantel A, Gabster B, Cheng J, Golomb H, Gajewski T . Severe hemophagocytic lymphohistiocytosis in a melanoma patient treated with ipilimumab + nivolumab. J Immunother Cancer. 2018; 6(1):73. PMC: 6048909. DOI: 10.1186/s40425-018-0384-0. View

16.

Wang D, Salem J, Cohen J, Chandra S, Menzer C, Ye F . Fatal Toxic Effects Associated With Immune Checkpoint Inhibitors: A Systematic Review and Meta-analysis. JAMA Oncol. 2018; 4(12):1721-1728. PMC: 6440712. DOI: 10.1001/jamaoncol.2018.3923. View

17.

Okawa S, Kayatani H, Fujiwara K, Ozeki T, Takada K, Iwamoto Y . Pembrolizumab-induced Autoimmune Hemolytic Anemia and Hemophagocytic Lymphohistiocytosis in Non-small Cell Lung Cancer. Intern Med. 2019; 58(5):699-702. PMC: 6443545. DOI: 10.2169/internalmedicine.1001-18. View

18.

Okada N, Kawazoe H, Takechi K, Matsudate Y, Utsunomiya R, Zamami Y . Association Between Immune-Related Adverse Events and Clinical Efficacy in Patients with Melanoma Treated With Nivolumab: A Multicenter Retrospective Study. Clin Ther. 2018; 41(1):59-67. DOI: 10.1016/j.clinthera.2018.11.004. View

19.

Crayne C, Albeituni S, Nichols K, Cron R . The Immunology of Macrophage Activation Syndrome. Front Immunol. 2019; 10:119. PMC: 6367262. DOI: 10.3389/fimmu.2019.00119. View

20.

Atteritano M, David A, Beninati C, Frisina A, Iaria C, Bagnato G . Haemophagocytic syndrome in rheumatic patients. A systematic review. Eur Rev Med Pharmacol Sci. 2012; 16(10):1414-24. View