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Abstract: SA-OR58

Posoleucel Associated with Reduction of BK Viremia and Persistence of BK-Reactive T Cells in a Phase 2 Trial

Session Information

Category: Transplantation

  • 2102 Transplantation: Clinical

Authors

  • Chandraker, Anil K., Brigham and Women's Hospital, Boston, Massachusetts, United States
  • Regmi, Anil, Inova Transplant Center, Falls Church, Virginia, United States
  • Gohh, Reginald Y., Rhode Island Hospital, Providence, Rhode Island, United States
  • Sharma, Akhil, UPMC, Pittsburgh, Pennsylvania, United States
  • Woodle, E. Steve, University of Cincinnati, Cincinnati, Ohio, United States
  • Ansari, Mohammed Javeed, Northwestern University, Evanston, Illinois, United States
  • Nair, Vinay, Northwell Health, New Hyde Park, New York, United States
  • Chen, Ling-Xin, University of California Davis, Davis, California, United States
  • Alhamad, Tarek, Washington University in St Louis School of Medicine, St Louis, Missouri, United States
  • Norman, Silas Prescod, University of Michigan, Ann Arbor, Michigan, United States
  • Cardarelli, Francesca, AlloVir Inc, Waltham, Massachusetts, United States
  • Ma, Julie, AlloVir Inc, Waltham, Massachusetts, United States
  • Gilmore, Sarah, AlloVir Inc, Waltham, Massachusetts, United States
  • Vasileiou, Spyridoula, AlloVir Inc, Waltham, Massachusetts, United States
  • Wojciechowski, David, The University of Texas Southwestern Medical Center, Dallas, Texas, United States
Background

Kidney transplant recipients (KTRs) with BK virus infection are at risk of nephropathy & graft loss. Posoleucel (PSL) is an off-the-shelf allogeneic multivirus-specific T cell therapy targeting BKV.

Methods

In this phase 2 double-blind study (NCT04605484), KTRs with BK viremia were randomized 1:1:1 to receive PSL cells wkly for 3 wks then q14 (PSL1) or q28 d (PSL2), or placebo (PBO) for 12 wks. Patients (pts) were followed for 12 wks after treatment. Primary objective was safety; secondary was plasma BK viral load (VL) reduction.

Results

Baseline (BL) characteristics of 61 dosed pts were similar across groups. No deaths, GVHD, or cytokine release syndrome were seen. 3 pts in PSL groups had graft rejection but none deemed treatment-related: 1 pt had history of rejection, 1 had renal TB, and 1 had rejection 68 d after last PSL dose. eGFR was stable in all groups. Table shows VL changes in 52 pts with stable immunosuppression (IS) in the 30 d before randomization who completed study. Superior antiviral effects were seen in both PSL groups vs PBO. Greatest effect on BK VL was at wk 24 in PSL1 pts with BK VL ≥10,000 cp/mL at screening: 75% (6/8) had a ≥1 log10 cp/mL decrease from BL (median -1.4 log) vs 25% (1/4) of PBO (-0.4 log). At BL most pts with high BK VL had no BK-specific T cell immunity. Over the 6 months after PSL infusion, circulating frequency of BK-reactive T cells increased vs PBO, more so in PSL1 group, coincident with VL reduction. PSL presence & persistence were confirmed by TCRvβ deep sequencing, with higher levels in pts with high VL.

Conclusion

PSL was generally safe & well tolerated. Clinically meaningful BK VL reductions & increases in BK-reactive T cells were seen in PSL pts, particularly those with high VL who are at highest risk for renal impairment.

Results at Wk 24 in Patients with Stable IS* before Randomization
EndpointPSL1
N=20
PSL2
N=18†
PBO
N=14‡
Pts w/ BK VL decreased by ≥1 log10 BKV DNA cp/mL vs BL, n (%)10 (50)5 (28)2 (14)
BK VL reduction from BL, median log10 BKV DNA cp/mL (min, max)-0.9
(-2.1, 0.1)
-0.45
(-1.8, 0.5)
-0.15
(-2.1, 0.3)
BK VL ≥50% reduction, n (%)17 (85)10 (56)6 (43)

*<50% IS reduction within 30 (+/-2) d of randomization. †2 pts lost to follow-up (LTFU) & 2 had IS reduction. ‡1 pt LTFU & 4 had IS reduction.