Oral Presentation ASSCR, AGCTS, ISCT ANZ and Friends Joint Scientific Conference 2019

Rapid administration of third-party cytomegalovirus (CMV), Epstein-Barr virus (EBV) or adenovirus (Adv) specific T-cells (VSTs) post-haemopoietic stem cell transplant (HSCT) (#31)

Wei Jiang 1 2 , Emily Blyth 1 2 3 , Selmir Avdic 1 3 , Gaurav Sutrave 1 2 3 , Leighton Clancy 2 3 , Caroline Bateman 4 , Peter Shaw 4 , Elissa Atkins 1 3 , Adrian Selim 5 , Vicki Antonenas 1 , David Collins 1 , David Ritchie 5 6 , David Gottlieb 1 2 3
  1. BMT and Cell Therapies Program, Westmead Hospital, Sydney, NSW, Australia
  2. Westmead Institute of Medical Research, Westmead, NSW, Australia
  3. Sydney Cellular Therapies Laboratory, Westmead, NSW, Australia
  4. Haematology Department, The Children's Hospital at Westmead, Sydney, NSW, Australia
  5. Bone Marrow Transplant Service, The Royal Melbourne Hospital, Melbourne, NSW, Australia
  6. The Peter MacCallum Cancer Centre, Melbourne, NSW, Australia

Introduction

Partially-HLA matched VSTs are safe and effective after failure of at least two weeks standard antiviral therapy to resolve viral infection. In this phase I trial, we assessed their safety when administered earlier in the course of viral infection post-HSCT.

 

Methods

A cell bank of VSTs was established from G-CSF mobilised peripheral blood from healthy donors. After stimulation with peptide mixes, VSTs were selected by expression of CD137 and cultured with cytokines. HSCT recipients were treated with up to 4 doses of 2x107of VST/m2commencing within 7 days of initial treatment for viral reactivation.

 

Results

A total of 188 doses of VST were manufactured from 7 donors with 12 product manufacturing runs (CMV n=3, EBV n=4 and Adv n=5). Median virus specificity was 75% for CMV, 83% for EBV and 37% for Adv. Thirty HSCT recipients were treated with VSTs within 7 days of initial antiviral treatment for viral reactivation at a median of 55 days post-transplant.  Data from 25 patients were available for analysis (CMV n=22, EBV n=2, Adv n=1). Median age was 58 (0-71).  18 patients received a single infusion, 6 received 2 and 1 received 4 infusions.  There were no immediate infusion-related toxicities. 23/25 patients (92%) had complete viral clearance (CR), 2 had a partial response (PR). Median time to best viral response was 20 days. There were 5 deaths (refractory aGVHD in 2 patients, pulmonary veno-occlusive disease/CMV pneumonitis, relapse of haematological malignancy, and sepsis/aspiration pneumonia).   Overall survival at a median 348 days follow up post-infusion (56-668) was 80%.

 

Conclusion

Early infusion of third-party donor partially HLA-matched VSTs for viral reactivation after HSCT is associated with no immediate toxicity, a low rate of graft-versus-host disease and complete viral clearance in 92% of recipients.

  • Have you presented your abstract at another international meeting?: No