Incidence and risk factors associated with a syndrome of persistent cytopenias after CAR-T cell therapy (PCTT)

Leuk Lymphoma. 2020 Apr;61(4):940-943. doi: 10.1080/10428194.2019.1697814. Epub 2019 Dec 3.

Abstract

Anti-CD19 Chimeric Antigen Receptor T cells (CAR-T) have shown dramatic efficacy in treating refractory aggressive B cell Lymphomas leading to FDA approval of axicabtagene ciloleucel and tisagenlecleucel. While long-term remission rate for both is higher than 33%, this treatment is associated with life-threatening complications including cytokine-release syndrome, encephalopathy, and lethal cerebral edema. Here we describe a case series of bone marrow failure syndromes with or without co-existing clonal myelodysplastic syndrome. Bone marrow failure was defined as absolute neutrophil count (ANC) <500 neutrophils/μL day 42 after infusion of CAR-T cells or filgrastim support to reach that number. We use "persistent cytopenias after T-cell therapy (PCTT)" to describe this syndrome which has an incidence of 38% with axicabtagene ciloleucel. Platelets <75,000/μL at the time of initiation of lymphodepleting chemotherapy and occurrence of maximum severity of cytokine-release syndrome (CRS) on day 0 or 1 after infusion of CAR-T cells are independent predictors of PCTT.

Keywords: CAR-T cells; bone marrow failure; cytokine release syndrome; lymphoma.

MeSH terms

  • Antigens, CD19 / therapeutic use
  • Biological Products
  • Bone Marrow Transplantation / adverse effects*
  • Cell- and Tissue-Based Therapy
  • Humans
  • Immunotherapy, Adoptive*
  • Incidence
  • Myelodysplastic Syndromes
  • Receptors, Chimeric Antigen*
  • Risk Factors
  • T-Lymphocytes
  • Treatment Outcome

Substances

  • Antigens, CD19
  • Biological Products
  • Receptors, Chimeric Antigen
  • axicabtagene ciloleucel