Durable immunity to EBV after rituximab and third-party LMP-specific T cells: a Children's Oncology Group study

Birte Wistinghausen, Center for Cancer and Blood Disorders, Children's National Hospital, Washington, DC.
Keri Toner, Center for Cancer and Blood Disorders, Children's National Hospital, Washington, DC.
Donald A. Barkauskas, Department of Population and Public Health Sciences, Keck School of Medicine of the University of Southern California, Los Angeles, CA.
Lauren P. Jerkins, Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN.
Hannah Kinoshita, Center for Cancer and Immunology Research, Children's National Research Institute, Children's National Hospital, Washington, DC.
Pamela Chansky, The George Washington University School of Medicine and Health Sciences, Washington, DC.
Gloria Pezzella, Center for Cancer and Immunology Research, Children's National Research Institute, Children's National Hospital, Washington, DC.
Lauren Saguilig, Children's Oncology Group Statistics and Data Center, Monrovia, CA.
Robert J. Hayashi, Division of Pediatric Hematology/Oncology, Department of Pediatrics, Washington University School of Medicine, St. Louis Children's Hospital, St. Louis, MO.
Harshal Abhyankar, Baylor College of Medicine, Texas Children's Hospital Cancer Center, Houston, TX.
Brooks Scull, Baylor College of Medicine, Texas Children's Hospital Cancer Center, Houston, TX.
Vivekanudeep Karri, Rush Medical College, Chicago, IL.
Jay Tanna, Center for Cancer and Immunology Research, Children's National Research Institute, Children's National Hospital, Washington, DC.
Patrick Hanley, Center for Cancer and Blood Disorders, Children's National Hospital, Washington, DC.
Michelle L. Hermiston, Department of Pediatrics, Benioff Children's Hospital and the Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA.
Carl E. Allen, Baylor College of Medicine, Texas Children's Hospital Cancer Center, Houston, TX.
Catherine M. Bollard, Center for Cancer and Blood Disorders, Children's National Hospital, Washington, DC.

Document Type

Journal Article

Publication Date

3-12-2024

Journal

Blood advances

Volume

8

Issue

5

DOI

10.1182/bloodadvances.2023010832

Abstract

Posttransplant lymphoproliferative disease (PTLD) in pediatric solid organ transplant (SOT) recipients is characterized by uncontrolled proliferation of Epstein-Barr virus-infected (EBV+) B cells due to decreased immune function. This study evaluated the feasibility, safety, clinical and immunobiological outcomes in pediatric SOT recipients with PTLD treated with rituximab and third-party latent membrane protein-specific T cells (LMP-TCs). Newly diagnosed (ND) patients without complete response to rituximab and all patients with relapsed/refractory (R/R) disease received LMP-TCs. Suitable LMP-TC products were available for all eligible subjects. Thirteen of 15 patients who received LMP-TCs were treated within the prescribed 14-day time frame. LMP-TC therapy was generally well tolerated. Notable adverse events included 3 episodes of rejection in cardiac transplant recipients during LMP-TC therapy attributed to subtherapeutic immunosuppression and 1 episode of grade 3 cytokine release syndrome. Clinical outcomes were associated with disease severity. Overall response rate (ORR) after LMP-TC cycle 1 was 70% (7/10) for the ND cohort and 20% (1/5) for the R/R cohort. For all cohorts combined, the best ORR for LMP-TC cycles 1 and 2 was 53% and the 2-year overall survival was 70.7%. vβT-cell receptor sequencing showed persistence of adoptively transferred third-party LMP-TCs for up to 8 months in the ND cohort. This study establishes the feasibility of administering novel T-cell therapies in a cooperative group clinical trial and demonstrates the potential for positive outcomes without chemotherapy for ND patients with PTLD. This trial was registered at www.clinicaltrials.gov as #NCT02900976 and at the Children's Oncology Group as ANHL1522.

Department

Pediatrics

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