Details

Autor(en) / Beteiligte

• 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.

Titel

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

Ist Teil von

• Blood advances, 2024-03, Vol.8 (5), p.1116-1127

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2024

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• •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.