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

• Published in: Transplantation and cellular therapy Vol. 28; no. 12; pp. 851.e1 - 851.e8
• Main Authors: Márquez-Algaba, Ester, Iacoboni, Gloria, Pernas, Berta, Esperalba, Juliana, Los Arcos, Ibai, Navarro, Victor, Monforte, Arnau, Beas, Francisco, Albasanz-Puig, Adaia, Carpio, Cecilia, Barba, Pere, Ruiz-Camps, Isabel
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.12.2022
• Subjects: Aggressive B cell lymphoma; CAR T cell therapy; Cytomegalovirus; Cytomegalovirus Infections - drug therapy; Cytomegalovirus replication; Cytomegalovirus surveillance; Dexamethasone - therapeutic use; Hematopoietic Stem Cell Transplantation - adverse effects; Humans; Immunotherapy, Adoptive - adverse effects; Lymphoma, B-Cell - complications; Receptors, Chimeric Antigen - therapeutic use; Aggressive B cell lymphoma; CAR T cell therapy; Cytomegalovirus surveillance; Cytomegalovirus replication
• ISSN: 2666-6367; 2666-6367
• DOI: 10.1016/j.jtct.2022.09.007

•Cytomegalovirus (CMV) replication is relatively frequent in patients with relapsed/refractory aggressive B cell lymphoma receiving chimeric antigen receptor (CAR) T cell therapy, but it is usually self-limited and not associated with end-organ disease.•Patients harboring CMV replication before CAR T cell infusion and/or receiving dexamethasone after infusion might benefit from active surveillance during the first weeks after infusion.•The clinical relevance of CMV replication in this setting is not clear. Management strategies should be tailored according to institutional guidelines and patient profile. 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.