Effective Treatment of a Melanoma Patient with Hemophagocytic Lymphohistiocytosis after Nivolumab and Ipilimumab Combined Immunotherapy

Abstract

Immune checkpoint inhibitors have significantly improved the prognosis of melanoma patients. However, these therapies may trigger unexpected immune-related adverse events (irAEs), which are challenging in making the proper diagnosis and providing treatment. Hematological toxicities are possible irAEs, but were poorly evaluated in clinical trials and treatment recommendations of this specific complications are limited. We present a stage IV melanoma patient who developed an extremely rare toxicity – hemophagocytic lymphohistiocytosis (HLH) after the 4th course of combined immunotherapy with nivolumab and ipilimumab. The patient was steroid resistant and only the treatment with various immunosuppressive agents provided control of the disease and finally melanoma regression. In this report, we evaluated the methods of HLH treatment and described our modification of available protocols. Immediate immunosuppression can be life-saving and due to rarity of this condition as well as lack of specific recommendations, every report is valuable for clinicians, especially when treatment was effective.

Early Effects of Nivolumab and Ipilimumab Combined Immunotherapy in the Treatment of Metastatic Melanoma in Poland: A Multicenter Experience

“…The high discontinuation rate due to AEs (almost 40% in our study) and too early treatment withdrawal (38% of patients received less than 4 series) despite the lack for PD seems to be the wrong strategy. Prompt AEs management and, if possible, immunotherapy continuation are important since they might improve the patient’s prognosis as we demonstrated in the case report from our clinic [ 43 ]. For example, a study from Nova Scotia demonstrated that only half of immunotherapy-related AEs are managed according to guidelines and about 17% of discontinued patients were withdrawn too early for this reason [ 44 ].…”

Auto-immune hemolytic anemia and hemophagocytic lymphohistiocytosis as immune-related adverse event in patients with metastatic melanoma and concurrent chronic lymphocytic leukemia: a case series and literature review

“…) Resolution AIHA, auto-immune hemolytic anemia; CLL, chronic lymphocytic leukemia; Dab/Tram, dabrafenib/trametinib; DAT, direct antigen test; HLH, hemophagocytic lymphohistiocytosis; ICI, immune checkpoint inhibitor; Ipi, ipilimumab; irAE, immune-related adverse event; MM, mycophenolate mofetil; Nivo, nivolumab; Pembro, pembrolizumab[17][18][19][20][21][22][23][24][25][26][27][28][29][30].…”