Preoperative pembrolizumab‑induced hemophagocytic lymphohistiocytosis in a patient with breast cancer: A case report

Kawamura,Yukino; Shimomura,Akihiko; Taniyama,Tomoko; Hirai,Hoshie; Hashimoto,Kazuki; Honda,Yayoi; Kitagawa,Dai; Nasu,Ryo; Shimazu,Hiroshi; Hangaishi,Akira; Shimizu,Chikako

doi:10.3892/ol.2025.14882

Preoperative pembrolizumab‑induced hemophagocytic lymphohistiocytosis in a patient with breast cancer: A case report

Authors:
- Yukino Kawamura
- Akihiko Shimomura
- Tomoko Taniyama
- Hoshie Hirai
- Kazuki Hashimoto
- Yayoi Honda
- Dai Kitagawa
- Ryo Nasu
- Hiroshi Shimazu
- Akira Hangaishi
- Chikako Shimizu
View Affiliations

Affiliations: Department of Breast Medical Oncology, National Center for Global Health and Medicine, Tokyo 162‑8655, Japan, Department of Breast Surgery, National Center for Global Health and Medicine, Tokyo 162‑8655, Japan, Department of Hematology, National Center for Global Health and Medicine, Tokyo 162‑8655, Japan
Published online on: January 9, 2025 https://doi.org/10.3892/ol.2025.14882
Article Number: 136
Copyright: © Kawamura et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Recently, the anti‑programmed cell death protein 1 antibody pembrolizumab, a type of immune checkpoint inhibitor (ICI), has been used in preoperative systemic chemotherapy for hormone receptor and human epidermal growth factor 2‑negative breast cancer, also known as triple‑negative breast cancer (TNBC). Chemotherapy with pembrolizumab has demonstrated clinical activity in terms of pathologic complete response and event‑free survival. Despite their efficacy, the current understanding of the full spectrum of side effects associated with relatively new ICIs remains incomplete. The present study describes a case of severe pembrolizumab‑induced hemophagocytic lymphohistiocytosis in a patient with early‑stage TNBC, and the strategies used to manage the patient in light of their pathophysiology.

View Figures

View References

1	Hudis CA and Gianni L: Triple-negative breast cancer: An unmet medical need. Oncologist. 16 (Suppl 1):S1–S11. 2011. View Article : Google Scholar
2	Cortazar P, Zhang L, Untch M, Mehta K, Costantino JP, Wolmark N, Bonnefoi H, Cameron D, Gianni L, Valagussa P, et al: Pathological complete response and long-term clinical benefit in breast cancer: The CTNeoBC pooled analysis. Lancet. 384:164–172. 2014. View Article : Google Scholar : PubMed/NCBI
3	Schmid P, Cortes J, Pusztai L, McArthur H, Kümmel S, Bergh J, Denkert C, Park YH, Hui R, Harbeck N, et al: Pembrolizumab for early triple-negative breast cancer. N Engl J Med. 382:810–821. 2020. View Article : Google Scholar : PubMed/NCBI
4	Schmid P, Cortes J, Dent R, Pusztai L, McArthur H, Kümmel S, Bergh J, Denkert C, Park YH, Hui R, et al: Event-free survival with pembrolizumab in early triple-negative breast cancer. N Engl J Med. 386:556–567. 2022. View Article : Google Scholar : PubMed/NCBI
5	Wang DY, Salem JE, Cohen JV, Chandra S, Menzer C, Ye F, Zhao S, Das S, Beckermann KE, Ha L, et al: Fatal toxic effects associated with immune checkpoint inhibitors: A systematic review and meta-analysis. JAMA Oncol. 4:1721–178. 2018. View Article : Google Scholar : PubMed/NCBI
6	Kramer R, Zaremba A, Moreira A, Ugurel S, Johnson DB, Hassel JC, Salzmann M, Gesierich A, Weppler A, Spain L, et al: Hematological immune related adverse events after treatment with immune checkpoint inhibitors. Eur J Cancer. 147:170–181. 2021. View Article : Google Scholar : PubMed/NCBI
7	Fardet L, Galicier L, Lambotte O, Marzac C, Aumont C, Chahwan D, Coppo P and Hejblum G: Development and validation of the HScore, a score for the diagnosis of reactive hemophagocytic syndrome. Arthritis Rheumatol. 66:2613–2620. 2014. View Article : Google Scholar : PubMed/NCBI
8	Henter JI, Horne A, Aricó M, Egeler RM, Filipovich AH, Imashuku S, Ladisch S, McClain K, Webb D, Winiarski J and Janka G: HLH-2004: Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer. 48:124–131. 2007. View Article : Google Scholar : PubMed/NCBI
9	Dupré A, Michot JM, Schoeffler A, Frumholtz L, Baroudjian B, Delyon J, Lebbe C and Lambotte O: Haemophagocytic lymphohistiocytosis associated with immune checkpoint inhibitors: A descriptive case study and literature review. Br J Haematol. 189:985–992. 2020. View Article : Google Scholar : PubMed/NCBI
10	Noseda R, Bertoli R, Müller L and Ceschi A: Haemophagocytic lymphohistiocytosis in patients treated with immune checkpoint inhibitors: Analysis of WHO global database of individual case safety reports. J Immunother Cancer. 7:1172019. View Article : Google Scholar : PubMed/NCBI
11	Planas R, Felber M, Vavassori S and Pachlopnik Schmid J: The hyperinflammatory spectrum: From defects in cytotoxicity to cytokine control. Front Immunol. 14:11633162023. View Article : Google Scholar : PubMed/NCBI
12	Brahmer JR, Abu-Sbeih H, Ascierto PA, Brufsky J, Cappelli LC, Cortazar FB, Gerber DE, Hamad L, Hansen E, Johnson DB, et al: Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immune checkpoint inhibitor-related adverse events. J Immunother Cancer. 9:e0024352021. View Article : Google Scholar : PubMed/NCBI
13	Michot JM, Lazarovici J, Tieu A, Champiat S, Voisin AL, Ebbo M, Godeau B, Michel M, Ribrag V and Lambotte O: Haematological immune-related adverse events with immune checkpoint inhibitors, how to manage? Eur J Cancer. 122:72–90. 2019. View Article : Google Scholar : PubMed/NCBI
14	Faleck DM, Dougan M, Tello M, Grossman JE, Moss AC and Postow MA: Accelerating the evolution of immune-related enterocolitis management. J Clin Oncol. 41:3110–3115. 2023. View Article : Google Scholar : PubMed/NCBI
15	Kurozumi A, Takahashi H, Watanabe T and Iwasaki Y: Two cases of lung cancer with hemophagocytic lymphohistiocytosis caused by immune checkpoint inhibitors. Thorac Cancer. 12:1625–168. 2021. View Article : Google Scholar : PubMed/NCBI
16	Sackstein P, Zaemes J and Kim C: Pembrolizumab-induced cytokine release syndrome in a patient with metastatic lung adenocarcinoma: A case report. J Immunother Cancer. 9:e0028552021. View Article : Google Scholar : PubMed/NCBI
17	Okawa S, Kayatani H, Fujiwara K, Ozeki T, Takada K, Iwamoto Y, Minami D, Sato K and Shibayama T: Pembrolizumab-induced autoimmune hemolytic anemia and hemophagocytic lymphohistiocytosis in non-small cell lung cancer. Intern Med. 58:699–702. 2019. View Article : Google Scholar : PubMed/NCBI
18	Laderian B, Koehn K, Holman C, Lyckholm L and Furqan M: Association of hemophagocytic lymphohistiocytosis and programmed death 1 checkpoint inhibitors. J Thorac Oncol. 14:e77–e78. 2019. View Article : Google Scholar : PubMed/NCBI
19	Honjo O, Kubo T, Sugaya F, Nishizaka T, Kato K, Hirohashi Y, Takahashi H and Torigoe T: Severe cytokine release syndrome resulting in purpura fulminans despite successful response to nivolumab therapy in a patient with pleomorphic carcinoma of the lung: A case report. J Immunother Cancer. 7:972019. View Article : Google Scholar : PubMed/NCBI
20	Hantel A, Gabster B, Cheng JX, Golomb H and Gajewski TF: Severe hemophagocytic lymphohistiocytosis in a melanoma patient treated with ipilimumab + nivolumab. J Immunother Cancer. 6:732018. View Article : Google Scholar : PubMed/NCBI
21	Satzger I, Ivanyi P, Länger F, Kreipe HH, Schaper-Gerhardt K, Beutel G, Cornberg M and Gutzmer R: Treatment-related hemophagocytic lymphohistiocytosis secondary to checkpoint inhibition with nivolumab plus ipilimumab. Eur J Cancer. 93:150–153. 2018. View Article : Google Scholar : PubMed/NCBI
22	Sadaat M and Jang S: Hemophagocytic lymphohistiocytosis with immunotherapy: Brief review and case report. J Immunother Cancer. 6:492018. View Article : Google Scholar : PubMed/NCBI
23	Takeshita M, Anai S, Mishima S and Inoue K: Coincidence of immunotherapy-associated hemophagocytic syndrome and rapid tumor regression. Ann Oncol. 28:186–189. 2017. View Article : Google Scholar : PubMed/NCBI
24	Malissen N, Lacotte J, Du-Thanh A, Gaudy-Marqueste C, Guillot B and Grob JJ: Macrophage activation syndrome: A new complication of checkpoint inhibitors. Eur J Cancer. 77:88–89. 2017. View Article : Google Scholar : PubMed/NCBI
25	Shah D, Shrestha R, Ramlal R, Hatton J and Saeed H: Pembrolizumab associated hemophagocytic lymphohistiocytosis. Ann Oncol. 28:14032017. View Article : Google Scholar : PubMed/NCBI