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

• Published in: Blood advances Vol. 8; no. 5; pp. 1116 - 1127
• Main Authors: Wistinghausen, Birte, Toner, Keri, Barkauskas, Donald A., Jerkins, Lauren P, Kinoshita, Hannah, Chansky, Pamela, Pezzella, Gloria, Saguilig, Lauren, Hayashi, Robert J., Abhyankar, Harshal, Scull, Brooks, Karri, Vivekanudeep, Tanna, Jay, Hanley, Patrick, Hermiston, Michelle L., Allen, Carl E., Bollard, Catherine M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 12.03.2024; The American Society of Hematology
• Subjects: Child; Clinical Trials and Observations; Epstein-Barr Virus Infections - complications; Epstein-Barr Virus Infections - drug therapy; Herpesvirus 4, Human; Humans; Lymphoproliferative Disorders - diagnosis; Lymphoproliferative Disorders - drug therapy; Lymphoproliferative Disorders - etiology; Rituximab - pharmacology; Rituximab - therapeutic use; T-Lymphocytes
• ISSN: 2473-9529; 2473-9537; 2473-9537
• DOI: 10.1182/bloodadvances.2023010832

•LMP-TC bank comprising 14 products with 11 distinct HLA restrictions was sufficient to match a diverse national pediatric population.•Durable LMP-TC responses were observed in ND pediatric patients with PTLD after incomplete response to rituximab. [Display omitted] 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.