S1641 INFECTIOUS COMPLICATIONS IN PATIENTS RECEIVING ANTI‐CD 19 CHIMERIC ANTIGEN RECEPTORS T‐CELLS (CAR T) FOR DIFFUSE LARGE B CELL LYMPHOMA (DLBCL). A MONOCENTRIC PRELIMINARY EXPERIENCE
Authors: R. Di Blasi, L. Aguinaga, J. Paillassa, M. Darmon, S. Bernard, E. Azoulay, M. Lafaurie, C. Thieblemont
Journal: HemaSphere (2019)

Background: Autologous anti‐CD19 chimeric antigen receptor (CD19 CAR) T‐cell immunotherapy showed significant benefit and satisfactory safety in relapsed/refractory DLBCL. Expected toxicities are neurologic events, cytokine release syndrome (CRS), hypogammaglobulinemia, cytopenias and B‐cell aplasia, the 3 latter being consequences of both CD19 CAR T‐cells and the lymphodepleting chemotherapy regimen (fludarabine+cyclophosphamide). Aims: Infectious complications during the first 30 days after CD19 CAR T‐cells infusion are not well defined yet. Differential diagnosis between fever and CRS might be difficult. The purpose of the present study is to evaluate infectious risk during treatment with CAR T‐cells. Methods: We retrospectively analyzed febrile events and infectious complications in 29 patients (pts) who received CAR T‐cells from June 1 st 2018 to January 31 st 2019 for R/R DLBCL. Pts were studied from day (D) 0, time of the injection, to D30. Results: Characteristics of pts are summarized in table 1. Mean age was 49.8 y.o. (23–77), 62% pts were male. A mean of 4 lines of treatment was previously administered (2–8). At admission, 83% of pts presented lymphopenia (≤1G/L, mean 0.43 G/L, 70–980). No grade (G) 3–4 neutropenia was observed before the beginning of lymphodepletion. Hypogammaglobulinemia was present in 28% of pts (mean 5 g/L, 2–11). Elevated C reactive protein before lymphodepletion was found in 55% pts (16/29) (mean 14 mg/L, 0–62). Anti‐pneumocystis prophylaxis was administered in 97% pts (28/29, 25 Cotrimoxazole, 3 Atovaquone), as well as antiviral prophylaxis (Valaciclovir). One pt suspended treatment without approval. Twenty‐four pts presented fever (83%), mean time of onset was D3 (0–13). 90% of pts presented neutropenia during the study period. Severe neutropenia (≤0.5G/L) was observed in 20/29 pts (70%) and mean duration was 6 days (2–19). 10% of the patients were still in severe neutropenia at D30. A microbiological documentation was found in 8 episodes occurring in 4 pts. For bacteria: 2 bloodstream infections (BSI) caused by Gram+ (1pt E.fecalis + S.epidermidis during cholangitis, 1 pt S.epidermidis with concomitant infection of indwelling catheter), 1 E.coli pneumonia and 1 C.difficilis enteritis. Antibacterial empirical treatment was administered in 22/24 pts presenting fever (92%). Mean duration of antibiotic treatment was 10 days (4–22). Four viral infections were observed: 1 Rhinovirus upper respiratory tract infection, 1 Norovirus enteritis and 1 pt presented CMV reactivation together with BK virus cystitis. No invasive fungal infections were observed. Only 2 pts received empiric systemic antifungal treatment. Hospitalization in intensive care unit was necessary for 10/29 pts (34%) and mean stay was 7 days (3–12). Only 2 out of 24 pts with a febrile event presented poor outcome at D30. In one pt death occurred because of disease progression and infection (BSI) and one pt had still positive CMV at D30 while receiving Foscarnet. No mortality was attributable to infectious complications alone. Summary/Conclusion: Febrile neutropenia is frequent in pts receiving CAR T‐cells and often cannot be distinguished from the onset of CRS. Diagnostic work‐up should be carried out following standard procedures. Bacterial and viral infection have low incidence and fungal infections did not occur in our population. Infectious complications appear mild and not fatal but broader studies deserve to be implemented to better define infectious risk in this subset of patients. image