Infectious events in patients treated for malignancies with T-cell engagers immunotherapies, a cohort study from the French REISAMIC registry.

Abstract

e24081 Background: Infectious complications were recently reported in patients (pts) receiving T-cell engager (TCE) therapy and require further investigations. Infections may result of depleting tumor-associated antigens, mobilizing immune T-cell compartment, or employing comedications like corticosteroids and/or anti-cytokine to manage cytokine release syndrome (CRS). This study aims to assess infectious events in patients undergoing TCE and to identify risk factors. Methods: Study design is a cohort study observational, nested in the French academic pharmacovigilance register, Registre des Effets Indésirables Sévères des Anticorps Monoclonaux Immunomodulateurs en Cancérologie (REISAMIC, CNIL number 2098694v0). All pts treated at Gustave Roussy (Villejuif, France), for all tumor indications except acute leukemia, were included. The primary objective was to report on infectious events and risk factors during TCE treatment. A competing-risk approach identify factors predisposing pts to infections with end of treatment as the competing event. Comedications with corticosteroids and anti-cytokine therapies associated with TCE were evaluated as a potential risk factor for infections. Results: Overall, 181 pts treated with TCE, median [range] age 62 [5-83] years, 64.1% male, median of 4 [1–11] prior lines of therapy (LOT), 118 (65.2%) with solid tumors and 63 (34.8%) with hematological (hem.) cancers, were included. CRS and neurological events (all grades), occurred in 111 (61,3%) and 11 (6,1%) of pts, respectively. The cumulative incidence of infections (all grades) was 29.8% (95% CI (22.1-38.0)) and 16.9% (95% CI (9.8-25.8)) for severe infections. Patients with hem. cancers, as compared with those with solid tumors, had significantly higher cumulative incidence of severe infections (35.3% vs. 7.6%.; p = 0.001). Six fatal infections (3.3%) occurred, all in pts with hem. cancers. The multivariable model found hem. cancer indications and > 3 prior LOT were associated with an increased risk of severe infections (HR = 3.11 [95% CI: 1.32–7.33], p = 0.009, and HR = 3.11 [95% CI: 1.19–8.06], p = 0.02, respectively). Comedications with corticosteroids or anti-cytokine therapies did not enhance the risk of infections. Microbiological distribution of pathogens unraveled hem. cancers pts were more infected by gram-negative bacteria, resistant gram-positive bacteria, and viral infections, as compared to solid tumors pts (p = 0.03; p = 0.08; and p = 0.02, respectively). Comprehensive microbiological map and sites of infections will be disclosed at the conference. Conclusions: Infectious events with TCE were primarily observed and severe in patients with hem. cancer. Comedications with corticosteroids or anti-cytokines did not enhance the risk of infections. Supportive care and preventive anti-infectious measures should be prioritized in patients at higher risk of infections.