Characteristics and recognition of early infections in patients treated with commercial anti-CD19 CAR-T cells

Eur J Haematol. 2022 Jan;108(1):52-60. doi: 10.1111/ejh.13712. Epub 2021 Oct 13.

Abstract

The characteristics of infections following chimeric antigen receptor T (CAR-T) cells targeting CD19 in real-word population are obscure. We analyzed infections' characteristics in the first month among consecutive patients with diffuse large B-cell lymphoma (DLBCL) (n = 60, median age, 69.3 years), treated with commercial CAR-T cells. ECOG performance status (PS) was 2-3 in most patients (58%). Infections were observed in 45% of patients (16, 27%, bacterial infections, and 14, 23%, viral infections). Bacterial infection included clinically documented infection in 7 (Pneumonia, n = 5; periodontal infection, n = 1; and cellulitis, n = 1) and microbiology documented infection (MDI) in 9 patients (Gram-negative rod, n = 5; Gram-positive cocci, n = 3, bacteremia; polymicrobial, n = 1). The most common viral infection was cytomegalovirus (CMV) reactivation (n = 10, 17%) leading to initiation of anti-CMV treatment in 6 (60%) among these patients. None had CMV disease. In univariate analysis, immune effector cell-associated neurotoxicity syndrome (ICANS) was associated with higher incidence of bacterial infection (OR=4.5, P = .018), while there was a trend for lower incidence of bacterial infections in patients with chemosensitive disease to bridging therapy (OR=0.375, P = .074). Age or PS was not associated with increased risk of bacterial infection. Increase in C-reactive protein (CRP) prior to fever onset was associated with microbiologically documented infections. We conclude that infections are common in the first month following CAR-T-cell administration, however, were not increased in elderly patients or those presenting with poorer PS. Increase in CRP prior to fever onset could support infection over cytokine release syndrome.

Keywords: CAR-T cells; infection; lymphoma.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, CD19 / immunology*
  • Bacterial Infections / diagnosis
  • Bacterial Infections / drug therapy
  • Bacterial Infections / etiology
  • Comorbidity
  • Disease Management
  • Disease Susceptibility
  • Female
  • Humans
  • Immunotherapy, Adoptive / adverse effects*
  • Immunotherapy, Adoptive / methods
  • Incidence
  • Infections / diagnosis
  • Infections / etiology*
  • Infections / therapy
  • Lymphoma, Large B-Cell, Diffuse / complications
  • Lymphoma, Large B-Cell, Diffuse / therapy
  • Male
  • Middle Aged
  • Odds Ratio
  • Receptors, Chimeric Antigen / immunology*
  • Risk Factors
  • Treatment Outcome
  • Young Adult

Substances

  • Antigens, CD19
  • Receptors, Chimeric Antigen