e13519 Background: The incidence of hypoG with recurrent infxs has rapidly increased in pts undergoing B-cell targeted therapies, including monoclonal and bispecific antibodies and chimeric antigen receptor (CAR) T-cell therapies, for benign and malignant diseases. These novel therapies produce life-threatening hypoG due to persistently severe depletion of B cells. The standard of care (SoC) for hypoG is intravenous immunoglobulin (IVIG) infusion, which is costly with limited efficacy. FFP is known to have B cell-related immunologic elements (IgM, A, & D) and complement that are essential for fighting infx. Methods: We retrospectively identified pts between January 2020 and 2024 diagnosed with hypoG who received FFP or IVIG for recurrent infx from B-cell targeted therapies (67% received anti-CD20 agents). Data was collected 12 months (mos) before and after FFP or IVIG infusion. HypoG-related recurrent infx are usually chronic with no documented positive cultures. Therefore, we reviewed each pt’s subjective reports of infectious improvement. Our primary endpoint was the annualized infx rate before and after FFP or IVIG, with a secondary outcome comparing hospitalization rates. Infxs were measured by courses of antimicrobial therapy. A Kaplan-Meier analysis was performed with accompanying log-rank testing for the primary outcome. Results: 21 pts met inclusion criteria, 5 received FFP and 16 received IVIG. Median (mdn) age was 72 years (range, 46 - 87) and 57.1% were female. 66.6% received FFP/IVIG after therapy for hematologic cancers (62% B cell lymphoma), 28.6% for solid tumors, and 4.8% for autoimmune disorders. The mdn number of infxs in the 12 mos preceding FFP and IVIG were 3 (2 - 5) and 3 (0 - 13), respectively, while the mdn number of infx-related hospitalizations prior to intervention was 2 (1 - 3) and 0 (0 - 6). The mdn number of infxs in the 12-mo period following FFP initiation was 1 (0 - 2) versus 0 (0 - 3) after IVIG initiation, and mdn number of infx-related hospitalizations post-intervention was 0 (0 - 1) and 2 (0 - 7). The mdn time to first infx on FFP and IVIG were 5 mos (2 - 12) and 4 mos (1 - 12), respectively, with one pt in each cohort not having an outcome. All 5 pts in the FFP cohort had documented subjective improvement of infectious symptoms after first infusion, as opposed to none in the IVIG cohort (p = 0.000). There was no significant difference in mdn time to first infx (p = 0.591). Conclusions: IVIG costs about 10,000 USD per infusion compared to 120 USD for FFP, excluding labor, distribution and facility charges. The estimated total IVIG market share in the US is about 5 billion in 2024. Replacement of IVIG with FFP will alleviate supply constraints and save US healthcare at least 4.95 billion USD yearly. Comparable rates of infx with FFP versus IVIG suggest that FFP is non inferior to the SoC for treating hypoG.