2097. Bacterial Infections in the Setting of Late Neutropenia Following CD19 Chimeric Antigen Receptor T-Cell (CAR-T) Therapy for Non-Hodgkin Lymphoma (NHL)
Authors: Little Jessica S , Hammond Sarah P , Jacobson Caron , Aleissa Muneerah M 
Published: December 2022

Abstract

Background
Cellular therapies such as CAR-T therapy have excellent clinical efficacy for treatment of relapsed and refractory hematologic malignancies. Late neutropenia, occurring more than 30 days after CAR-T cell infusion, is a frequent complication, though its impact on infection risk is not well understood.

Methods
We performed a retrospective study of 280 adults receiving CD19 CAR-T therapy for NHL between December 2017 and September 2021 (n=280). Levofloxacin prophylaxis was used after CAR-T infusion until initial count recovery (absolute neutrophil count (ANC) ≥ 1000). Patients were evaluated for late neutropenia with ANC &lt; 1000 during three time periods following cell infusion: day 30 – 100; day 100 – 365; and after day 365. Infections were recorded if there was a microbiologic diagnosis with correlating symptoms and treatment. Infection severity was determined using Blood and Marrow Transplant Clinical Trials Network criteria. Patients were censored on the first day of any additional antineoplastic therapy after relapse, death or last follow up until 1/25/2022.

Results
Of 280 patients with NHL who received CAR-T therapy, 116 (41%) had late neutropenia. Baseline characteristics and early CAR-T toxicities are shown in Table 1. Amongst patients with late neutropenia, 11 (9%) developed a bacterial infection during late neutropenia and 3 (3%) developed Clostridioides difficile infection. The most frequent infection site was the bloodstream (n=5), followed by the urinary tract (UTI; n=4). Most infections were moderate in severity (n = 9, 64%), though several were serious (Severe=4; Life-threatening=1). Median time from CAR-T therapy to bacterial infection was 70 days (range 30 - 584); 10 occurred among 99 at risk during day 30-100 (10%), 3 among 39 at risk during day 101-365 (8%), and 1 among 12 at risk after day 365 (8%). All but one of the severe or life-threatening infections occurred prior to Day 100. Characteristics and timing of individual infections are outlined in Table 3. Table 3.Characteristics and Timing of Individual Bacterial Infections

Conclusion
Bacterial infections were relatively uncommon in patients with late neutropenia after CD19 CAR-T therapy for NHL in the absence of antibacterial prophylaxis and most severe infections in this population occurred between day 30 and 100. Further studies are needed to inform optimal prevention strategies.

Disclosures
Sarah P. Hammond, MD, F2G: Advisor/Consultant|F2G: Grant/Research Support|GSK: Grant/Research Support|Scynexis: Grant/Research Support Caron Jacobson, MD, MMSc, Abintus Bio: Advisor/Consultant|Bluebird Bio: Advisor/Consultant|BMS/Celgene: Advisor/Consultant|Daiichi-Sankyo: Advisor/Consultant|Epizyme: Advisor/Consultant|ImmPACT Bio: Advisor/Consultant|Instill Bio: Advisor/Consultant|Ipsen: Advisor/Consultant|Kite/Gilead: Advisor/Consultant|Kite/Gilead: Grant/Research Support|Lonza: Advisor/Consultant|Novartis: Advisor/Consultant|Pfizer: Grant/Research Support.