Incidence and Characteristics of Respiratory Viral Infections after CAR T-Cell Therapy

This is the authors' abstract. We don't add key points for this paper.

Chimeric antigen receptor (CAR) T-cell therapy has altered the treatment of lymphoid malignancies, but it is associated with acute toxicities and so-called "on-target, off-tumor" effects that place patients at risk for infectious complications. Respiratory viral infections (RVIs) are a common, but poorly characterized complication of CAR T-cell therapy. To describe the incidence, characteristics, and outcomes of patients with RVIs after CAR T-cell therapy. We retrospectively reviewed the records of adults at Duke University Hospital who received CD19-targeted CAR T-cell therapy between 4/2018 and 10/2021. Microbiologically confirmed RVIs occurring within the first 18 months after CAR T-cell therapy are described. Baseline characteristics and clinical outcomes of patients who developed an RVI are compared to those who did not. Of 66 patients who met inclusion criteria, 13 (19.7%) had 15 RVIs within 18 months of CAR T-cell therapy. The median time from CAR T-cell therapy to RVI diagnosis was 311 days (IQR 116.5, 415), with 10 (66.7%) occurring after 180 days. SARS-CoV-2 and RSV accounted for the majority of RVIs (46.7% and 26.7%, respectively), and rhinovirus was identified in 20%. Most cases were mild in severity (73.3%) and there were no deaths attributable to RVI. Upper respiratory tract infections comprised the majority of RVIs (66.7%), but lower respiratory tract infections were responsible for all four moderate or severe RVIs. Compared to those who did not develop an RVI, patients who developed an RVI were younger (median 57 vs 64 years; p=0.017) and had a lower Charlson Comorbidity Index (median 3 vs 4; p=0.048), but there were otherwise no significant differences in baseline characteristics. Patient outcomes were similar and although the RVI group had lower 30-day and 18-month mortality following CAR T-cell therapy, the difference was not statistically significant (0% vs 8%, p=0.30; 23% vs 43%, p=0.18). No differences in acute CAR T-cell therapy-related toxicities were identified, with high rates of cytokine release syndrome (RVI: 92%, no RVI: 81%; p=0.33) and neurotoxicity (RVI: 46%, no RVI: 45%; p=0.95) in both groups. We found that RVIs are a common infectious complication after CAR T-cell therapy. RVIs predominantly occurred late (>180 days) post-CAR T-cell therapy in contrast to other infectious complications. Additional studies are needed to understand risk factors and prevention strategies for RVIs in this population.