ANHL1522: Durable Immunity to EBV post Rituximab and Third Party LMP-specific T-cells: A Children's Oncology Group Study

Birte Wistinghausen, Children's National Medical Center, Washington, District of Columbia, United States.
Keri Toner, Children's National Health System, Washington, District of Columbia, United States.
Donald A. Barkauskas, University of Southern California, United States.
Lauren P. Jerkins, Children's National Hospital, United States.
Hannah Kinoshita, Childrens National Medical Center, Washington, District of Columbia, United States.
Pamela Chansky, 3. The George Washington University School of Medicine and Health Sciences, United States.
Gloria Pezzella, Children's National Hospital, Washington, District of Columbia, United States.
Lauren Saguilig, Children's National Hospital, United States.
Robert J. Hayashi, Washington University in St. Louis School of Medicine, St. Louis, Missouri, United States.
Harshal A. Abhyankar, Baylor College Of Medicine, Houston, Texas, United States.
Brooks Scull, Baylor College of Medicine, Houston, Texas, United States.
Vivekanudeep Karri, Baylor College of Medicine, Houston, Texas, United States.
Jay Tanna, Childrens National Medical Center, Washington, District of Columbia, United States.
Patrick J. Hanley, Children's National Medical Center, Washington, District of Columbia, United States.
Michelle L. Hermiston, University of California, San Francisco, San Francisco, California, United States.
Carl E. Allen, Baylor College of Medicine, Houston, Texas, United States.
Catherine M. Bollard, Children's National Hospital, United States.

Document Type

Journal Article

Publication Date

1-1-2024

Journal

Blood advances

DOI

10.1182/bloodadvances.2023010832

Abstract

Post-transplant lymphoproliferative disease (PTLD) in pediatric solid organ transplant (SOT) recipients is characterized by uncontrolled proliferation of Epstein Barr virus infected (EBV+) B cells in an environment of decreased immune function. This study was conducted to evaluate the feasibility, safety, clinical and immunobiological outcomes in pediatric SOT patients with PTLD treated with rituximab followed by third-party latent-membrane-protein-specific T-cells (LMP-TC). Newly diagnosed (ND) patients without complete response to rituximab induction and all relapsed/refractory (R/R) patients were assigned to arm LMP-TC. 15/18 enrolled patients were assigned to LMP-TC. Suitable LMP-TC products were available for all eligible subjects and 13 of 15 patients who received LMP-TC were treated within the prescribed 14-day time frame. LMP-TC therapy was generally well-tolerated. Notable adverse events included three episodes of rejection in cardiac transplant recipients occurring during LMP-TC therapy that were attributed to sub-therapeutic immunosuppression and one episode of Grade III cytokine release syndrome. Clinical outcomes were associated with disease severity. Overall response rate (ORR) following LMP-TC cycle 1 was 70% (7/10) for the ND cohort and 20% (1/5) for the R/R cohort. The best ORR for all subjects across cohorts for LMP-TC cycle 1 and 2 was 53%. Two-year OS was 70.7% for the entire study. vT-cell receptor sequencing showed persistence of adoptively transferred third-party LMP-TC for up to 8 months in the ND cohort. This study establishes the feasibility of administering novel T-cell therapies upfront in a cooperative group clinical trial and demonstrates the potential for positive outcomes without chemotherapy for ND patients with PTLD. NCT02900976 Children's Oncology Group Identifier: ANHL1522 ANHL1522: A Pilot Study of Rituximab (RTX) and Third Party Latent Membrane Protein (LMP)-Specific Cytotoxic T-Lymphocytes (LMP-TC) in Pediatric Solid Organ Recipients (SOT) With EBV-Positive CD20-Positive Post-Transplant Lymphoproliferative Disease (PTLD).

Department

Pediatrics

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