Chimeric antigen receptor T-cell therapy: Foundational science and clinical knowledge for pharmacy practice

J Oncol Pharm Pract. 2019 Jul;25(5):1217-1225. doi: 10.1177/1078155219836480. Epub 2019 Mar 19.

Abstract

The Food and Drug Administration has recently approved two autologous chimeric antigen receptor T-cell immunotherapies tisagenlecleucel (Kymriah™) and axicabtagene ciloleucel (Yescarta™) for patients with advanced lymphocytic malignancies. Both immunotherapies target the CD19-positive B-cell neoplasms. Kymriah™ is indicated for the treatment of relapsed or refractory acute lymphoblastic leukemia and large B-cell lymphoma. Yescarta™ is indicated for lymphoma only. Although the new therapy offers a promise for patients with advanced disease, it is associated with adverse events including neurotoxicity and cytokine release syndrome, which can be fatal and may require a high level of multidisciplinary supportive care. Due to the risks, both Kymriah™ and Yescarta™ are subject to Risk Evaluation and Mitigation Strategy (REMS) protocols. As active members of multidisciplinary clinical teams, pharmacists are likely to be responsible for the execution of Kymriah™ and Yescarta™ REMS programs. This manuscript describes foundational science and clinical knowledge of chimeric antigen receptor T-cell immunotherapies, common therapy-specific toxicities and REMS requirements for Kymriah™ and Yescarta™ in relation to practice of pharmacy.

Keywords: Tisagenlecleucel; axicabtagene ciloleucel; chimeric antigen receptor T-cell therapy; cytokine release syndrome; risk evaluation and mitigation strategy; tocilizumab.

MeSH terms

  • Antigens, CD19 / adverse effects
  • Antigens, CD19 / therapeutic use*
  • Biological Products
  • Hematologic Neoplasms / drug therapy*
  • Humans
  • Immunotherapy, Adoptive / adverse effects
  • Knowledge
  • Lymphoma, B-Cell / drug therapy
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Receptors, Antigen, T-Cell / immunology
  • Receptors, Antigen, T-Cell / therapeutic use*
  • Receptors, Chimeric Antigen / immunology

Substances

  • Antigens, CD19
  • Biological Products
  • Receptors, Antigen, T-Cell
  • Receptors, Chimeric Antigen
  • tisagenlecleucel
  • axicabtagene ciloleucel