P1397: third-party multivirus-specific t cells for the treatment of refractory viral infections after hematopoietic stem cell transplantation

Topic: 25. Gene therapy, cellular immunotherapy and vaccination - Clinical Background: Although hematopoietic stem cell transplantation (HSCT) is a curative treatment for a variety of diseases, refractory viral infections post-HSCT are rare, life-threatening conditions due to the deficient T-cell response and lacking effective treatment options. Aims: We present the data of 16 patients who were treated in 3 different transplantation centers between 2018-2022 and received the same VST product for various (CMV, EBV, BKV) refractory viral infections after HSCT. Methods: We define refractory viral infection as the unresponsiveness to the first-line treatment such as rituximab for EBV, cidofovir for BKV, and gancyclovir for CMV patients. Viral loads were measured by PCR. “Clearance of viremia/viruria” was used for the viral load under the threshold and “decrease of viremia/viruria” was used for any reduction in the viral load. Adverse events are defined according to common terminology criteria for adverse events (CTCAE) version 5.0, 2017. We produced the third-party multi-specific (CMV, EBV, ADV, BKV) VST cells according to our patented process (PT201901625/PY201900446). For the third-party production, we were searching for at least ≥1 HLA matching. After leukapheresis, CD 45RA was depleted and VST cells were proliferated with the induction of both direct peptides and antigen-presenting cells. The viral peptides were supplied by MACS GMP PepTivator AdV5 Hexon, BKV VP1, EBV Select, and HCMV pp65. All the patients received the standard single dose of 2x107 VST cells/m2. Results: The characteristics and outcomes of the patients were described in Table-1. The median viral load (viruria) of the BKV patients was 6x109 copy/ml (2x109-14x109 copy/ml) and hemorrhagic cystitis was accompanied for every patient. All the BKV patients responded at least with decreasing viremia, hemorrhagic cystitis was cleared for all, and clearance of viremia was noted for one patient. The median viral load of EBV patients was 1,5x104 copy/ml (2x103-3,5x104 copy/ml). One of the EBV patients responded with a clearance of viremia, 2 patients experienced a decrease of viremia and one patient did not respond. The median viral load of CMV patients was 2,5x104 copy/ml (9x103-14x106 copy/ml) and retinitis was detected in one patient with vision impairment. Five patients experienced a decrease in viremia and the patient with retinitis had a clinical response, but 2 of the CMV patients did not respond. There was no significant association between the response rate and the initial viral load. Two patients had GvHD which was under control before the VST infusion and none of them deteriorated after the VST infusion. There were no serious adverse events in our study. Graft versus host disease after VST infusion was not observed. In our study group, there was no treatment-related mortality, 9 patients were deceased in a median of 6 months (2-25 months) after HSCT and 7 patients were alive with a median of 28 months (7-53 months) on follow-up. Summary/Conclusion: Our study indicates that the third-party VST application for refractory viral infections after HSCT was safe. Our overall response rate (total 80%, clearance of viremia 20%) was promising. Especially, a 100% response rate with full clinical improvement in BKV patients was noteworthy. Keywords: Hematopoietic stem cell replication, EBV, Cellular therapy, CMV