Posoleucel in Kidney Transplant Recipients with BK Viremia
Authors: Chandraker Anil , Regmi Anil , Gohh Reginald , Sharma Akhil , Woodle E. Steve , Ansari Mohammed J. , Nair Vinay , Chen Ling-Xin , Alhamad Tarek , Norman Silas , Cibrik Diane , Singh Manpreet , Alper Arnold , Jain Divya , Zaky Ziad , Knechtle Stuart , Sharfuddin Asif , Gupta Gaurav , Lonze Bonnie E. , Young Jo-Anne H. , Adey Deborah , Faravardeh Arman , Dadhania Darshana M. , Rossi Ana P. , Florescu Diana , Cardarelli Francesca , Ma Julie , Gilmore Sarah , Vasileiou Spyridoula , Jindra Peter T. , Wojciechowski David 
Published: March 2024

Key Points

Posoleucel was generally safe, well tolerated, and associated with a greater reduction of BK viremia compared with placebo.BK viremia reduction occurred coincident with an increase in the circulating frequency of BK virus–specific T cells in posoleucel recipients.The presence and persistence of posoleucel was confirmed by T-cell receptor variable β sequencing.

Background
Kidney transplant recipients with BK virus infection are at risk of developing BK virus–associated nephropathy, allograft rejection, and subsequent graft loss. There are no approved treatments for BK virus infection. Posoleucel is an off-the-shelf, allogeneic, multivirus-specific T-cell investigational therapy targeting BK virus, as well as five other opportunistic viruses: adenovirus, cytomegalovirus, Epstein–Barr virus, human herpesvirus 6, and John Cunningham virus.

Methods
In this phase 2, double-blind study, kidney transplant recipients with BK viremia were randomized 1:1:1 to receive posoleucel weekly for 3 weeks and then every 14 days (bi-weekly dosing) or every 28 days (monthly dosing) or placebo for 12 weeks. Participants were followed for 12 weeks after completing treatment. The primary objective was safety; the secondary objective was plasma BK viral load reduction.

Results
Sixty-one participants were randomized and dosed. Baseline characteristics were similar across groups. No deaths, graft-versus-host disease, or cytokine release syndrome occurred. The proportion of patients who had adverse events (AEs) judged by the investigators to be treatment-related was slightly lower in recipients of posoleucel: 20% (4 of 20 patients) and 18% (4 of 22) in those infused on a bi-weekly and monthly schedule, respectively, and 26% (5 of 19) in placebo recipients. None of the grade 3–4 AEs or serious AEs in any group were deemed treatment-related. No deaths, graft-versus-host disease, or cytokine release syndrome occurred. Three participants had allograft rejection, but none were deemed treatment-related by investigators. In posoleucel recipients, BK viremia reduction was associated with an increase in the circulating frequency of BK virus–specific T cells, and the presence and persistence of posoleucel was confirmed by T-cell receptor sequencing.

Conclusions
Posoleucel was generally safe, well tolerated, and associated with a larger reduction of BK viremia compared with placebo. Limitations of this study include the relatively short duration of follow-up and lack of power to detect significant differences in clinical outcomes.

Clinical Trial registry name and registration number:
Study of Posoleucel (Formerly Known as ALVR105; Viralym-M) in Kidney Transplant Patients With BK Viremia, NCT04605484.