Experimental T-cell therapy shows promise against six viral infections common after stem cell transplants

Posoleucel, an investigational allogeneic off-the-shelf T-cell therapy that simultaneously targets six different viruses, demonstrated promising antiviral efficacy and safety in a phase II study of patients who had undergone stem cell transplantation to treat their cancer or other blood diseases.

In this trial the researchers evaluated the safety and efficacy of posoleucel. The trial enrolled 58 adult and pediatric patients who had undergone allo-SCT to treat cancers or other diseases of the blood and had infections of at least one of the six viruses that posoleucel is designed to target. Eligible patients were either unresponsive to or unable to tolerate standard therapies for these viruses. In total, there were 70 viral infections in the trial population, the majority of which were CMV and BK virus infections.

Fifty-five of 58 patients (95 percent) had responses to posoleucel within six weeks of infusion, and the amount of circulating virus was reduced by an average of 97 percent in these patients. Among the 12 patients who had more than one viral infection, 10 patients (83 percent) had a response against the viruses with which they were infected.

Responses were defined as reduction of viral load to normal range with resolution of clinical signs and symptoms (complete response), or as a viral load reduction of at least 50 percent or a 50 percent improvement of clinical signs and symptoms (partial response).

Responses against specific viruses were as follows:

Adenovirus: 83 percent of 12 patients had a response within six weeks.

BK virus: 100 percent of 27 patients had a response within six weeks.

CMV: 96 percent of 24 patients had a response within six weeks.

Epstein-Barr virus: 100 percent of two patients had a response within six weeks.

Human herpes virus 6: Three of four patients responded and viral load was reduced in all four patients.

JC virus: The one patient with JC virus infection experienced initial stabilization of viral symptoms; however, symptoms ultimately progressed, and the patient died.

No patients experienced cytokine release syndrome. Thirteen patients (22 percent) reported acute graft-versus-host disease (GvHD); however, only four of these cases were considered de novo cases, as nine patients had been diagnosed with GvHD prior to posoleucel treatment. Only three patients reported acute GvHD grade 2 or higher. The most common GvHD symptoms were skin flares, which were successfully treated in the majority of cases.

Reference:

Bilal Omer et al,Posoleucel, an Allogeneic, Off-the-Shelf Multivirus-Specific T-Cell Therapy, for the Treatment of Refractory Viral Infections in the Post-HCT Setting,Clinical Cancer Research,doi 10.1158/1078-0432.CCR-22-2415