# Immunoglobulin Replacement Therapy and Infectious Complications After CD19-Targeted CAR-T-Cell Therapy

> **NIH NIH R01** · FRED HUTCHINSON CANCER CENTER · 2024 · $858,502

## Abstract

PROJECT SUMMARY/ABSTRACT
Chimeric antigen receptor T cell therapy (CARTx) has transformed treatment for B cell malignancies. However,
the effects of CARTx on humoral immunity and infection risk are incompletely understood. The high prevalence
of hypogammaglobulinemia in CARTx recipients has driven frequent use of prophylactic immunoglobulin G (IgG)
replacement therapy (IGRT) to prevent infections in this patient population. However, limited data exist to support
this practice, and shortages, side effects, and cost necessitate careful stewardship of IGRT. Emerging data
indicate that pathogen-specific antibodies often persist after CD19-CARTx, potentially contesting the need for
IGRT. Well controlled studies are needed to ascertain the clinical utility of IGRT in CARTx recipients. Within this
clinical context, other important and connected questions remain about how IGRT affects CAR-T cell function,
in addition to the possible costs versus benefits of the effect of IGRT on healthcare resource utilization.
This timely and unique proposal will be the first randomized, controlled trial of IGRT use in CARTx recipients and
provide critical insights into the potential risks and benefits of IGRT in this patient population. The key objectives
of this study are to evaluate whether IGRT in CARTx recipients reduces infection rates compared to placebo,
and to understand the impact of IGRT on previously unexplored outcomes such as CAR-T cell expansion, CAR-
T cell persistence, CAR-T cell function, and healthcare resource utilization. For the proposed study, we have
assembled an interdisciplinary group of physicians and scientists from high-volume CARTx centers who will
leverage our expertise in immuno-oncology, infectious diseases, and cancer outcomes research.
We propose a randomized trial of IGRT versus placebo in 150 adults with serum total IgG ≤400 mg/dL prior to
CD19-CARTx. Participants will be randomized 1:1 to receive IGRT or placebo within 14 days prior to CARTx
and at 28-day intervals after CARTx for 4 months. Aim 1 will compare between study arms the incidence rate of
infections through 6 months after CD19-CARTx; we will also longitudinally characterize and compare total and
pathogen-specific IgG levels and their association with infections. Aim 2 will explore the association of IGRT with
healthcare resource utilization, cytokine release syndrome, and CARTx-associated neurotoxicity. Aim 3 will
characterize the impact of IGRT on CAR-T cell expansion, persistence, and function.
This will be the first randomized controlled study of IGRT after CARTx and will provide foundational data to
establish evidence-based estimates of the clinical efficacy and risk-benefit of IGRT in CD19-CARTx recipients.
In parallel, this study will explore other potential effects of IGRT on CAR-T cell dynamics and healthcare resource
utilization. The data generated by this proposal will provide the groundwork for future studies to refine infection
prevention strategies in the gro...

## Key facts

- **NIH application ID:** 10915043
- **Project number:** 5R01CA276040-02
- **Recipient organization:** FRED HUTCHINSON CANCER CENTER
- **Principal Investigator:** Joshua Aiden Hill
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $858,502
- **Award type:** 5
- **Project period:** 2023-09-01 → 2028-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10915043

## Citation

> US National Institutes of Health, RePORTER application 10915043, Immunoglobulin Replacement Therapy and Infectious Complications After CD19-Targeted CAR-T-Cell Therapy (5R01CA276040-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10915043. Licensed CC0.

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