Impact of Cytomegalovirus Replication in Patients with Aggressive B Cell Lymphoma Treated with Chimeric Antigen Receptor T Cell Therapy

Transplant Cell Ther. 2022 Dec;28(12):851.e1-851.e8. doi: 10.1016/j.jtct.2022.09.007. Epub 2022 Sep 20.

Abstract

Data are scarce on cytomegalovirus (CMV) replication in patients receiving CD19-directed chimeric antigen receptor (CAR) T cell treatment. Here we describe the incidence, severity, and management of CMV infection in patients with aggressive B cell lymphoma treated with CAR T cell therapy. In this retrospective observational study, we analyzed CMV viral load and its clinical impact in patients with aggressive B cell lymphoma receiving CAR T cell therapy between July 2018 and December 2021 at a single center. Patients with a negative baseline CMV IgG or a previous allogeneic stem cell transplantation were excluded. CMV replication was determined in whole blood. Overall, 105 patients met the study's inclusion criteria. Ten patients presented with CMV replication before CAR T cell infusion and were analyzed separately. Forty-two of the remaining 95 patients (44%) had at least 1 positive CMV determination, with a viral load ≥1000 IU/mL in 21 patients (22%). Four patients in the main cohort (N = 95) and 4 patients in the preinfusion replication group (N = 10) achieved a viral load >10,000 IU/mL. Only 7 patients received preemptive antiviral treatment. No CMV end-organ disease was reported. The sole independent risk factor associated with CMV viremia ≥1000 IU/mL was dexamethasone treatment (odds ratio, 8.4; 95% confidence interval, 2.4 to 36.6; P = .002). Based on our findings, we designed an algorithm for CMV management in this setting. CMV replication is relatively frequent in patients with aggressive B cell lymphoma receiving CAR T cell therapy. It is usually self-limited and not associated with end-organ disease. Patients receiving dexamethasone or harboring CMV replication before infusion might benefit from active surveillance and preemptive treatment strategies.

Keywords: Aggressive B cell lymphoma; CAR T cell therapy; Cytomegalovirus replication; Cytomegalovirus surveillance.

Publication types

  • Observational Study

MeSH terms

  • Cytomegalovirus
  • Cytomegalovirus Infections* / drug therapy
  • Dexamethasone / therapeutic use
  • Hematopoietic Stem Cell Transplantation* / adverse effects
  • Humans
  • Immunotherapy, Adoptive / adverse effects
  • Lymphoma, B-Cell* / complications
  • Receptors, Chimeric Antigen* / therapeutic use

Substances

  • Receptors, Chimeric Antigen
  • Dexamethasone