Posoleucel, an investigational off-the-shelf T-cell therapy, showed promising safety and efficacy for eradicating multiple viruses in a phase 2 study of patients who previously underwent allogeneic stem cell transplant (allo-SCT).
Of 58 adult and pediatric patients with a total of 70 viral infections at the time of enrollment in the open-label trial, 55 (95%) had a treatment response within 6 weeks of infusion with posoleucel, and the amount of circulating virus was reduced by an average of 97%, Thomas Pfeiffer, MD, and colleagues reported.
In 12 patients who had more than one viral infection, 10 (83%) had a response against each of the viruses, researchers noted.
The responses were defined as a reduction of viral load to normal range with complete response, or as a viral load reduction of at least 50 percent or a partial response.
The findings were published online in Clinical Cancer Research.
Specifically, the treatment evoked responses to adenovirus in 83% of 12 affected patients, BK virus in all 27 affected patients, CMV in 96% of 24 affected patients, Epstein-Barr virus in both affected patients, and human herpes virus in 75% of 4 patients. Additionally, one patient with JC virus experienced initial stabilization of viral symptoms, although the symptoms ultimately progressed, and the patient died.
“The key finding is that 95% of patients whose infections had been refractory to conventional therapies responded to posoleucel with corresponding reductions in viral load and with limited rates of GvHD [graft-versus-host disease],” Dr. Pfeiffer, a pediatric cancer specialist at Washington University in St. Louis, explained in a prepared statement. “Overall, posoleucel was found to be very effective and had a favorable safety profile in a highly vulnerable patient population.”
“Another exciting observation from this study was that posoleucel could be administered within 24 hours in some cases, with symptom resolution in a matter of days in some patients,” added senior author Bilal Omer, MD, a pediatric hematologist-oncologist at Texas Children’s Hospital and Baylor College of Medicine, Houston. “It was quite impressive how quickly patients could be treated.”
Dr. Omer explained that currently available treatments for patients who develop viral infections after allo-SCT have numerous limitations, including toxicities such as myelosuppression or kidney injury and limited efficacy.
In this study, 13 patients (22% percent) reported acute GvHD, but only 4 of the cases were considered de novo cases; 9 patients had been diagnosed with GvHD prior to posoleucel treatment. The most common GvHD symptoms were skin flares, which were successfully treated in the majority of cases, Dr. Omer explained.
No patients experienced cytokine release syndrome.
“The ability to target six viruses with a single therapy would be beneficial for patients with multiple viral infections,” he said, adding that posoleucel is the first T-cell therapy in development for BK virus, which can cause severe bladder infections.
Posoleucel utilizes healthy donor T cells rather than the patient’s or transplant donor’s T cells, which circumvents the lengthy development process of more customized therapies and allows for earlier treatment of viral infections, he noted.
The investigators are currently evaluating posoleucel in randomized phase 3 clinical trials to confirm these findings.
This study was supported by the National Heart, Lung, and Blood Institute Production Assistance for Cellular Therapies; Conquer Cancer Foundation/American Society for Clinical Oncology; the Dan L. Duncan Comprehensive Cancer Center; and the National Institutes of Health.
Dr. Omer disclosed pending patent applications for engineered T-cell therapies unrelated to this study, and he has received research funding from AlloVir, which manufactures posoleucel. Dr. Pfeiffer declared no conflicts of interest.
This story originally appeared on MDedge.com, part of the Medscape Professional Network.
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