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Nivolumab–induced encephalitis post allogeneic stem cell transplant in a patient with Hodgkin’s disease

Bone Marrow Transplantation volume 54, pages 749–751 (2019)Cite this article

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Immune check-point inhibitors (CPI) represent a novel therapeutic strategy for the treatment of solid and haematologic malignancies [1]. Tumour cells are able to evade immune surveillance and CPIs act by blocking negative regulatory components on T-cells, thus enhancing their activity against tumour cells [2]. Nivolumab, a humanised IgG4 kappa monoclonal antibody that acts against the programmed cell death 1 (PD-1) receptor in T-cells, was approved in 2016 for relapsed or refractory Hodgkin lymphoma (HL) after haematopoietic stem cell transplantation (HCT) [3]. Neurologic immune-related adverse reactions (IRARs) after treatment with CPI have previously been reported, most commonly with the CTLA-4 inhibitor ipilimumab [4]. Here, we report the first detailed description of nivolumab associated autoimmune encephalitis in a patient with relapsed Hodgkin lymphoma after allogenic HCT.

A 28-year-old female was admitted with 2 weeks of worsening headaches. She had a medical history of HL with infiltration of the spleen, bones and lung diagnosed in 2014. She failed multiple rounds of chemotherapy prior to autologous HCT in October 2015 with complete remission until 2016, then she relapsed again and received 4 cycles of brentuximab vedotin, achieving complete remission, followed by matched unrelated allogeneic HCT in June 2016 with a preparative regimen of clofarabine, busulfan, and gemcitabine. Her post-transplant course was complicated by GVHD of the liver treated with prednisone from February through May 2017. She relapsed 9 months after the allogeneic HCT and achieved complete clinical remission after 8 cycles of brentuximab vedotin, only to relapse again in December 2017. She then started therapy with escalating doses of nivolumab 80 mg on day 1 in February 2018, followed by a second dose of 120 mg (2 mg/kg) on day 14. She was not on any other immunosuppressants at this time. The patient reported that a few days following the first dose of nivolumab she started experiencing headaches that resembled migraines but were relieved with aspirin. After the second dose of nivolumab, the headaches worsened and were associated with nausea and dizziness. On day 22, the patient presented to clinic with severe frontal headaches and was referred to the emergency department for concern of possible meningitis. On admission, she was afebrile, alert but apathetic with mild clouding of consciousness. Physical examination was positive for photophobia but negative for nuchal rigidity, Kernig and Brudzinsky signs. No oral lesions, systemic skin lesions, heart murmur or abdominal tenderness were observed.

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Author notes

  1. These authors contributed equally: Alejandro De la Hoz, Farnaz Foolad

Authors and Affiliations

  1. Grupo de Investigación en Enfermedades Infecciosas, Hospital Universitario San Ignacio, Pontificia Universidad Javeriana, Bogotá, DC, Colombia

    Alejandro De la Hoz

  2. Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Alejandro De la Hoz, Cinthia Gallegos & Dimitrios P. Kontoyiannis

  3. Division of Pharmacy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Farnaz Foolad

  4. Division of Infectious Diseases, Department of Internal Medicine, University of Texas Health Science Center at Houston, Houston, TX, USA

    Cinthia Gallegos

  5. Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Steven Kornblau

Authors
  1. Alejandro De la Hoz
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Correspondence to Dimitrios P. Kontoyiannis.

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De la Hoz, A., Foolad, F., Gallegos, C. et al. Nivolumab–induced encephalitis post allogeneic stem cell transplant in a patient with Hodgkin’s disease. Bone Marrow Transplant 54, 749–751 (2019). https://doi.org/10.1038/s41409-018-0363-6

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