Third-Party BK Virus-Specific Cytotoxic T Lymphocyte Therapy for Hemorrhagic Cystitis Following Allotransplantation. Issue 24 (20th August 2021)

• Record Type: Journal Article
• Authors: 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;
• Is Part Of: Journal of clinical oncology. Volume 39:Issue 24(2021)
• Page Start: 2710
• Page End: 2719
• Publication Date: 2021-08-20
• Subjects: Oncology -- Periodicals; Cancer -- Periodicals; Oncology; Medical Oncology; Cancérologie -- Périodiques; Cancer -- Périodiques; Cancérologie; Cancer; Oncology; Oncologia; Càncer; Periodicals; 616.994
• DOI: 10.1200/JCO.20.02608
• Languages: English
• ISSNs: 0732-183X

Abstract

Abstract : 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.