e19004 Background: Prolonged hypogammaglobulinemia is a common side effect of CD19 chimeric antigen receptor (CAR) T-cell therapy for B-NHL. Average infection rates 1 year (yr) post CAR-T are 44-53% (Kampouri, Tran Infect Dis 2023). Prophylactic IVIG is typically dosed by weight; however, optimal dosing strategy remains unknown. We explored the efficacy of reduced flat IVIG dose on infection rates and non-relapse mortality (NRM) post CAR-T. Methods: B-NHL pts who received commercial CD19 CAR-T therapy from Nov 2017 to Mar 2023 at Vanderbilt Medical Center were included. All pts were on trimethoprim-sulfamethoxazole and valacyclovir for prophylaxis. IVIG at a flat dose of 10 grams was given for IgG &lt; 400 mg/dL. Relevant clinical variables were collected from day 30 to 1 yr. Infections were defined as mild (treated outpatient), moderate (required admission), or severe (required intensive care unit) and by CTCAE v5 criteria. Severe neutropenia was defined as ANC&lt;500 and severe lymphopenia was ALC&lt;500. NRM was defined by death without progression or relapse. Estimated cost of therapy was $140/gram of IVIG based on previously published data. Results: A total of 43 pts (35 large cell lymphoma, 7 mantle cell lymphoma, and 1 follicular lymphoma) with median follow up of 445 days (range 134-2141) were included. Axicabtagene ciloleucel was given to 34 pts (79%), tisagenlecleucel to 2 pts (5%), and brexucabtagene autoleucel to 7 pts (16%). Median age was 58 (range 22-81). Median number of pre CAR-T therapies was 3 (range 1-7). There were 52 total infections with median time to first infection of 165 days (range 31-365). Of all infections, 21 (40%) were viral, 29 (56%) bacterial, and 2 (4%) fungal. There were 31 (60%) mild infections, 19 (36%) moderate, and 2 (4%) severe. Multiple G≥3 infections occurred in 14 pts (33%). At first infection, 4 pts (10%) had severeneutropenia and 13 pts (31%) had severelymphopenia. IVIG was given to 27 pts (63%). Median IgG at D30 was 438 mg/dL (range 143–1099) and 414 mg/dL (range 133–842) at D60. Prolonged IgG≤400 at 6 months occurred in 15 pts (35%). Median IVIG cost using flat dosing was $2800 (range $0-12,600) compared to a median cost of $8,075 (range $0-76,642) if weight-based dosing was utilized. NRM was 9% (4 pts). Of those pts, only 1 had a G≥3 infection during the first-year post CAR-T. Conclusions: We demonstrate comparable infection rates 1 yr post CD19 CAR-T and low NRM with the use of 10g flat IVIG dosing for consecutively treated pts. In addition, only 1 of 4 pts with NRM had severe infection within 1 yr. Notably, 35% of pts had persistent hypogammaglobulinemia at 6 mo and use of a flat dosing schedule provided substantial cost reduction. These findings should be validated in a prospective randomized trial.

Flat dose intravenous immunoglobulin (IVIG) for primary infection prophylaxis after CAR-T for B-cell non-Hodgkin lymphoma (B-NHL).