Infection epidemiology in relation to different therapy phases in patients with haematological malignancies receiving CAR T-cell therapy

Abstract Background: We described the real-life epidemiology and causes of infections on the different therapy phases in patients with haematological malignancies undergoing chimeric antigen receptor (CAR) T-cells directed towards CD19+ or BCMA+ cells. Methods: All consecutive patients receiving CAR T-cell therapy at our institution were prospectively followed-up. We performed various comparative analyses of all patients and subgroups with and without infections. Results: 91 adults mainly received CAR T-cell therapy for acute leukemia (53%) and lymphoma (33%). We documented a total of 77 infections in 47 (52%) patients, 37 (48%) during the initial neutropenic phase and 40 (52%) during the non-neutropenic phase. Infections during the neutropenic phase were mainly due to bacterial (29, 78%): catheter infections (11 [38%] cases), endogenous source (5 [17%]), and Clostridiodes difficile (5 [17%]). Viral and fungal infections accounted for 14% and 8% of infections. Those patients receiving corticosteroids after CAR T-cell therapy had a higher risk of endogenous infection (100% vs 16%; p=0.006). During the non-neutropenic phase, bacterial infections remained very frequent (24, 60%), mainly with catheter source (8, 33%). Respiratory tract infections were common (17, 43%), frequently caused by viruses (14, 82%). There were no documented differences in patients with and without infections in this phase. Conclusions: Infections after CAR T-cell therapy were frequent. During the neutropenic phase, it is essential to prevent nosocomial infections and balance the use of antibiotics to lower endogenous bacteraemia and Clostridial infection rates. It is also mandatory to improve preventive strategies for viral respiratory tract infections in later therapy phases.