Nivolumab may be a promising therapy among adults with relapsed or refractory Epstein-Barr virus (EBV)-associated hemophagocytic lymphohistiocytosis (HLH), according to research published in Blood.1

EBV-positive HLH, a subtype of secondary HLH, is most frequently diagnosed in adolescence and adulthood, and carries a poor prognosis. While standard treatments include dexamethasone and etoposide, chemotherapy prevents the immune system from effectively working against EBV infection, which may permit eventual relapse, leaving allo–hematopoietic stem cell transplantation as the only curative option.

Nivolumab, a programmed death protein-1 (PD-1) inhibitor, has been approved for the treatment of multiple cancers, including EBV-positive gastric cancer, and may work to treat both HLH and the underlying causal viral infection. For this retrospective analysis, researchers reviewed data from 7 patients treated with nivolumab for relapsed/refractory EBV-HLH to determine its effectiveness in this setting.

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Among the 7 patients, the median age was 25 years (range, 15-36), 4 were male, and 3 were female; all patients showed signs of aggressive disease. All patients received prior chemotherapy, with a median duration of primary treatment of 19.6 weeks (range, 6.3-72).

Six of the 7 patients responded to nivolumab, with 5 reaching a clinical complete response (CR). Four of the 5 patients with a CR also reached molecular complete response, and all 5 patients with a clinical CR were in remission for more than 40 weeks after a median follow-up of 16 months (range, 11.4-18.9). One patient did not respond.

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No grade 3 or worse adverse events were noted. While plasma EBV load decreased in 4 of the 5 patients with a CR, 4 also had a persistent or elevated fever for 1 to 2 weeks, and transient cytopenias and increased serum ferritin/sCD25 levels were also reported.

“In conclusion, our study suggests that nivolumab can achieve sustained control of [relapsed/refractory] EBV-HLH with tolerable toxicity,” the authors wrote. “Furthermore, serological and intracellular negative conversion of EBV-DNA suggests that PD-1 blockade has the potential to cure the disease without allo–[hematopoietic stem cell transplantation].


  1. Liu P, Pan X, Chen C, et al. Nivolumab treatment of relapsed/refractory Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis in adults. Blood. 2020;135(11):826-833.