TY - JOUR
T1 - Third-Party BK Virus-Specific Cytotoxic T Lymphocyte Therapy for Hemorrhagic Cystitis Following Allotransplantation
AU - Olson, Amanda
AU - Lin, Ruitao
AU - Marin, David
AU - Rafei, Hind
AU - Bdaiwi, Mustafa H.
AU - Thall, Peter F.
AU - Basar, Rafet
AU - Abudayyeh, Ala
AU - Banerjee, Pinaki
AU - Aung, Fleur M.
AU - Kaur, Indresh
AU - Abueg, Glorette
AU - Rao, Sheetal
AU - Chemaly, Roy
AU - Mulanovich, Victor
AU - Al-Atrash, Gheath
AU - Alousi, Amin M.
AU - Andersson, Borje S.
AU - Anderlini, Paolo
AU - Bashir, Qaiser
AU - Castro, Karla M.
AU - Daher, May
AU - Galvan, Isabel M.
AU - Hosing, Chitra
AU - Im, Jin S.
AU - Jones, Roy B.
AU - Kebriaei, Partow
AU - Khouri, Issa
AU - Mehta, Rohtesh
AU - Molldrem, Jeffrey
AU - Nieto, Yago
AU - Oran, Betul
AU - Popat, Uday
AU - Qazilbash, Muzaffar
AU - Rondon, Gabriela
AU - Saini, Neeraj
AU - Spencer, Bryan
AU - Srour, Samer
AU - Washington, Dominique
AU - Barnett, Melissa
AU - Champlin, Richard E.
AU - Shpall, Elizabeth J.
AU - Rezvani, Katayoun
N1 - Publisher Copyright:
© 2021 by American Society of Clinical Oncology.
PY - 2021/8/20
Y1 - 2021/8/20
N2 - PURPOSE BK virus-associated hemorrhagic cystitis (BKV-HC) is a common complication of allogenic hematopoietic stem cell transplantation (AHSCT), particularly in recipients of alternative donor transplants, which are being performed in increasing numbers. BKV-HC typically results in painful hematuria, urinary obstruction, and renal dysfunction, without a definitive therapeutic option. 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.
AB - PURPOSE BK virus-associated hemorrhagic cystitis (BKV-HC) is a common complication of allogenic hematopoietic stem cell transplantation (AHSCT), particularly in recipients of alternative donor transplants, which are being performed in increasing numbers. BKV-HC typically results in painful hematuria, urinary obstruction, and renal dysfunction, without a definitive therapeutic option. 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.
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U2 - 10.1200/JCO.20.02608
DO - 10.1200/JCO.20.02608
M3 - Article
C2 - 33929874
AN - SCOPUS:85110432243
SN - 0732-183X
VL - 39
SP - 2710
EP - 2719
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 24
ER -