Advertisement

Relationship between clinical course of nivolumab-related myositis and immune status in a patient with Hodgkin’s lymphoma after allogeneic hematopoietic stem cell transplantation

  • Takahiro Kobayashi
  • Yong-mei Guo
  • Takaya Yamashita
  • Miho Nara
  • Tomoko Yoshioka
  • Yoshihiro Kameoka
  • Takahiro Fukuda
  • Naoto Takahashi
Case Report

Abstract

Although programmed cell death (PD)-1 blockade induces immune-related adverse events (irAEs), little is known about the safety of PD-1 blockade after allogeneic hematopoietic stem cell transplantation (HSCT). Here, we describe immune system changes during nivolumab-related myositis in a patient with Hodgkin’s lymphoma after allogeneic HSCT; to our knowledge, this is the first such report in the literature. At the onset of myositis, the patient lost lower limb mobility against gravity, and had an activated immune profile with increased cytotoxic CD107a and granzyme B expression, as well as pro-inflammatory cytokines, interferon-γ, tumor necrosis factor-α, interleukin-2 in T and NK cells compared to healthy donor. Pulse steroid therapy decreased creatine kinase levels and induced PD-1 expression and regulatory T cells, but did not improve myositis; previously activated markers remained high. Four-week corticosteroid therapy decreased previously activated markers and the myositis improved. These findings provide new insights into nivolumab-induced irAE pathogenesis and suggest possible optimal treatments for irAEs.

Keywords

Graft-versus-host disease Nivolumab Immune-related adverse events Myositis Hodgkin’s lymphoma 

Notes

Compliance with ethical standards

Conflict of interest

N.T. received grants from Ono Pharmaceutical. The other authors declare no conflict of interest.

Supplementary material

12185_2018_2584_MOESM1_ESM.docx (19 kb)
Supplementary material 1 (DOCX 19 KB)

References

  1. 1.
    Stucci S, Palmirotta R, Passarelli A, Silvestris E, Argentiero A, Lanotte L, et al. Immune-related adverse events during anticancer immunotherapy: pathogenesis and management. Oncol Lett. 2017;14:5671–80.Google Scholar
  2. 2.
    Miyara M, Yoshioka Y, Kitoh A, Shima T, Wing K, Niwa A, et al. Functional delineation and differentiation dynamics of human CD4+ T cells expressing the FoxP3 transcription factor. Immunity. 2009;30:899–911.CrossRefGoogle Scholar
  3. 3.
    Weber JS, Kahler KC, Hauschild A. Management of immune-related adverse events and kinetics of response with ipilimumab. J Clin Oncol. 2012;30:2691–7.CrossRefGoogle Scholar
  4. 4.
    Calandra T, Bernhagen J, Metz CN, Spiegel LA, Bacher M, Donnelly T, et al. MIF as a glucocorticoid-induced modulator of cytokine production. Nature. 1995;377:68–71.CrossRefGoogle Scholar
  5. 5.
    Waage A, Bakke O. Glucocorticoids suppress the production of tumour necrosis factor by lipopolysaccharide-stimulated human monocytes. Immunology. 1988;63:299–302.Google Scholar
  6. 6.
    Dornmair K, Goebels N, Weltzien HU, Wekerle H, Hohlfeld R. T-cell-mediated autoimmunity: novel techniques to characterize autoreactive T-cell receptors. Am J Pathol. 2003;163:1215–26.CrossRefGoogle Scholar
  7. 7.
    Matsuoka KI. Low-dose interleukin-2 as a modulator of Treg homeostasis after HSCT: current understanding and future perspectives. Int J Hematol. 2018;107:130–7.CrossRefGoogle Scholar
  8. 8.
    Mathian A, Jouenne R, Chader D, Cohen-Aubart F, Haroche J, Fadlallah J, et al. Regulatory T cell responses to high-dose methylprednisolone in active systemic lupus erythematosus. PLoS One. 2015;10:e0143689.CrossRefGoogle Scholar
  9. 9.
    Herbaux C, Gauthier J, Brice P, Drumez E, Ysebaert L, Doyen H, et al. Efficacy and tolerability of nivolumab after allogeneic transplantation for relapsed Hodgkin lymphoma. Blood. 2017;129:2471–8.CrossRefGoogle Scholar
  10. 10.
    Haverkos BM, Abbott D, Hamadani M, Armand P, Flowers ME, Merryman R, et al. PD-1 blockade for relapsed lymphoma post-allogeneic hematopoietic cell transplant: high response rate but frequent GVHD. Blood. 2017;130:221–8.CrossRefGoogle Scholar

Copyright information

© Japanese Society of Hematology 2019

Authors and Affiliations

  1. 1.Department of Hematology, Nephrology and RheumatologyAkita University Graduate School of MedicineAkitaJapan
  2. 2.Clinical Research Promotion and Support CenterAkita University HospitalAkitaJapan
  3. 3.Department of Hematopoietic Stem Cell TransplantationNational Cancer Center HospitalTokyoJapan

Personalised recommendations