Third-Party BK Virus-Specific Cytotoxic T Lymphocyte Therapy for Hemorrhagic Cystitis Following Allotransplantation.
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Olson Amanda, Lin Ruitao, Marin David, Rafei Hind, Bdaiwi Mustafa H, Thall Peter F, Basar Rafet, Abudayyeh Ala, Banerjee Pinaki, Aung Fleur M, Kaur Indresh, Abueg Glorette, Rao Sheetal, Chemaly Roy, Mulanovich Victor, Al-Atrash Gheath, Alousi Amin M, Andersson Borje S, Anderlini Paolo, Bashir Qaiser, Castro Karla M, Daher May, Galvan Isabel M, Hosing Chitra, Im Jin S, Jones Roy B, Kebriaei Partow, Khouri Issa, Mehta Rohtesh, Molldrem Jeffrey, Nieto Yago, Oran Betul, Popat Uday, Qazilbash Muzaffar, Rondon Gabriela, Saini Neeraj, Spencer Bryan, Srour Samer, Washington Dominique, Barnett Melissa, Champlin Richard E, Shpall Elizabeth J, Rezvani Katayoun
Аннотация
METHODS: We performed a clinical trial (ClinicalTrials.gov identifier: NCT02479698) to assess the feasibility, safety, and efficacy of administering most closely HLA-matched third-party BKV-specific cytotoxic T lymphocytes (CTLs), generated from 26 healthy donors and banked for off-the-shelf use. The cells were infused into 59 patients who developed BKV-HC following AHSCT. Comprehensive clinical assessments and correlative studies were performed.
RESULTS: Response to BKV-CTL infusion was rapid; the day 14 overall response rate was 67.7% (40 of 59 evaluable patients), which increased to 81.6% among evaluable patients at day 45 (40 of 49 evaluable patients). No patient lost a previously achieved response. There were no cases of de novo grade 3 or 4 graft-versus-host disease, graft failure, or infusion-related toxicities. BKV-CTLs were identified in patient blood samples up to 3 months postinfusion and their in vivo expansion predicted for clinical response. A matched-pair analysis revealed that, compared with standard of care, after accounting for prognostic covariate effects, treatment with BKV-CTLs resulted in higher probabilities of response at all follow-up timepoints as well as significantly lower transfusion requirement.
CONCLUSION: Off-the-shelf BKV-CTLs are a safe and effective therapy for the management of patients with BKV-HC after AHSCT.