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Case Reports
. 2018 Jul 16;6(1):73.
doi: 10.1186/s40425-018-0384-0.

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

Andrew Hantel  1 , Brooke Gabster  2 , Jason X Cheng  3 , Harvey Golomb  1 , Thomas F Gajewski  4
Affiliations
Case Reports

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

Andrew Hantel et al. J Immunother Cancer. .

Abstract

Background: 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.

Case presentation: 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.

Conclusions: 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.

Keywords: Checkpoint inhibitor; HLH; Hemophagocytosis; Immune checkpoint; Melanoma.

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Conflict of interest statement

Ethics approval and consent to participate

Not applicable: this is not a research clinical trial, consent for use and publication of patient data was obtained as below.

Consent for publication

Patient consent was obtained and can be requested separately as per the submission guidelines.

Competing interests

TFG has received research funding from Bristol-Myers Squibb, the manufacturer of ipilimumab and nivolumab.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Laboratory value trends over time. Time of hospitalization is shaded. Units of blood are marked correspondingly as “PRBC.” Period of steroid administration is noted along the X-axis. Ferritin, hemoglobin, and bilirubin levels are noted
Fig. 2
Fig. 2
Bone marrow biopsy obtained at diagnosis. a. Necrotic melanoma cells; H&E, magnification of 500×. b. Phagocytosing histiocytes containing red blood cells; H&E, magnification of 500×, blue arrows. c. Phagocytosing histiocytes containing red blood cells, higher magnification. D-F. Immunohistochemistry for CD3 (D), CD8 and CD4 (E), and CD68 (F); magnification of 200×
Fig. 3
Fig. 3
Bone marrow biopsy obtained after disease resolution. a Regenerative BM core, H&E, magnification of 500×. b BM aspirate smears showing erythroid hyperplasia with no neoplastic cells. Wright-Giemsa, magnification of 500×. Immunohistochemistry for CD34 (c) and Melan-A (d). There was no increase in CD34+ blasts, and no detectable Melan-A-positive cells, i.e. no melanoma; magnification 200×
See this image and copyright information in PMC

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