Posoleucel, an Allogeneic, Off-the-Shelf Multivirus-Specific T-Cell Therapy, for the Treatment of Refractory Viral Infections in the Post-HCT Setting

Abstract

Purpose: Viral infections are a major cause of morbidity and mortality following allogeneic hematopoietic cell transplantation (allo-HCT). In the absence of safe and effective antiviral treatments, virus-specific T cells have emerged as a promising therapeutic option. Posoleucel is a multivirus-specific T-cell therapy for off-the-shelf use against six viral infections that commonly occur in allo-HCT recipients: adenovirus, BK virus (BKV), cytomegalovirus, Epstein–Barr virus, human herpes virus-6, and JC virus. Patients and Methods: We conducted an open-label, phase II trial to determine the feasibility and safety of posoleucel in allo-HCT recipients infected with one or more of these viruses. Infections were either unresponsive to or patients were unable to tolerate standard antiviral therapies. Fifty-eight adult and pediatric patients were enrolled and treated. Results: Posoleucel was well tolerated, with no cytokine release syndrome or other infusion-related toxicities; two patients (3.4%) developed Grade 2 and one patient (1.7%) Grade 3 GvHD during the trial. The overall response rate 6 weeks after the first posoleucel infusion was 95%, with a median plasma viral load reduction of 97%. Of the 12 patients who had two or more target viral infections identified at study entry, 10 (83%) had a clinical response for all evaluable viruses. Of the 23 patients treated for refractory BKV-associated hemorrhagic cystitis, 74% had resolution of symptoms and macroscopic hematuria by 6 weeks post-infusion. Conclusions: In this open-label trial, treatment of refractory viral infections/disease in allo-HCT recipients with posoleucel was feasible, safe, and effective.

On behalf of the SFGM‐TC: Real‐life use of third‐party virus‐specific T‐cell transfer in immunocompromised transplanted patients

“…Antiviral therapies are associated with consistent side effects such as acute kidney injury or hematotoxicity that might worsen the overall prognosis 6–9 . For adenovirus (AdV), 10–12 cytomegalovirus (CMV), 13,14 and Epstein Barr virus (EBV), virus‐specific T‐cells (VST) have been developed as an alternate therapy, 15,16 since the pioneering work of Pr Riddell et al in 1992 and international colleagues afterward 17–22 …”

“…[6][7][8][9] For adenovirus (AdV), [10][11][12] cytomegalovirus (CMV), 13,14 and Epstein Barr virus (EBV), virus-specific T-cells (VST) have been developed as an alternate therapy, 15,16 since the pioneering work of Pr Riddell et al in 1992 and international colleagues afterward. [17][18][19][20][21][22] Since 2016, France approved AdV-VST, EBV-VST, or CMV-VST production in the Cell Therapy Unit of the University Hospital of Nancy (UTCT) as Advanced Therapy Medicinal Products (ATMP). Twenty-nine consecutive patients with AdV, EBV, or CMV replications/infections, persisting despite an optimized antiviral therapy, were infused.…”

Adenovirus infection in allogeneic hematopoietic cell transplantation

“…All the infusions were well tolerated and no patient had infusion‐related toxicities. In two patients (3.4%) and one patient (1.7%), a grade II and grade III GVHD flare was recorded in the postinfusion period 69 . Currently, this cellular product (Posoleucel) is under assessment in phase III studies for the treatment and prevention of CMV, EBV, AdV, HHV‐6, and BKPyV infections.…”

Infections after chimeric antigen receptor (CAR)‐T‐cell therapy for hematologic malignancies

“…Novel therapies, including pathogen‐targeted monoclonal antibodies, cytotoxic T‐cell and natural killer (NK) cell‐based immunotherapies are emerging and may play a role in future prevention and treatment strategies 102–107 …”