Investigational T-cell Therapy for Viral Infections After Allogeneic Stem Cell Transplant Showed 95% Patient Response

An investigational allogeneic off-the-shelf T-cell therapy, posoleucel (Viralym-M, ALVR105), can defend against 6 common viruses that can occur following a stem cell transplant, according to investigators who published a recent study in Clinical Cancer Research, a journal for the American Association for Cancer Research (AACR). Among participants in the trial, 95% responded to posulecuel within 6 weeks of infusion, reducing the virus in circulation by an average of 97%.

“The ability to target 6 viruses with a single therapy would be beneficial for patients with multiple viral infections,” said senior author Bilal Omer, MD, a pediatric hematologist-oncologist at Texas Children’s Hospital, and an assistant professor of pediatrics and member of the Dan L Duncan Comprehensive Cancer Center at Baylor College of Medicine, in a recent press release.

The viruses posoleucel targets include BK virus, adenovirus, cytomegalovirus (CMV), Epstein-Barr virus, human herpes virus 6, and JC virus. The first of these viruses can cause severe and excruciatingly painful bladder infections.

An allogeneic stem cell transplantation (allo-SCT), which can be used for patients with blood cancers or hematologic disorders, is a process by which a patient’s stem cells are replaced with a donor’s stem cells. But, as Pfeiffer explains, the process can be riddled with risks—one of the main hazards to the patient is increased susceptibility to viral infections, which is linked with high mortality and morbidity.

Currently, the treatments available carry their own risks as well. Antiviral medications, for instance, may have difficult-to-tolerate toxicities such as myelosuppression or kidney injury, explained Omer.

“Moreover, their efficacies are limited in this patient population, and treatment resistance develops relatively easily,” Omer said in the press release.

In a phase 2 trial, researchers identified 58 adult and pediatric patients who were treated with allo-SCT and infected with 1 of the 6 target viral strains. The patients did not respond to standard therapies that combat these viruses, which primarily target CMV and BK.

Within 6 weeks during the trial, responses to posoleucel were seen among 83% of patients with adenovirus, 100% of patients with BK virus, 96% of patients with CMV, 100% of patients with Epstein-Barr, 75% of patients with human herpes virus, and initially in the sole patient who contracted JC virus.

Among participants, 13% reported acute graft-versus-host disease (GVHD)—whose main symptom is skin flares— but only 4 of these cases occurred at the beginning of treatment. GVHD cases were mainly acute and below grade 2, and there were no reports of cytokine release syndrome.

“It was quite impressive how quickly patients could be treated,” Omer said.

The investigators noted that since the study was a single-arm trial, the results would be limited by this. To investigate posoleucel further, a randomized phase 3 trial is currently underway.

“Overall, posoleucel was found to be very effective and had a favorable safety profile in a highly vulnerable patient population,” said first author Thomas Pfeiffer, MD, an assistant professor of pediatrics at Washington University School of Medicine in St. Louis, in the press release.

Reference

Omer B. An Investigational T-cell Therapy Shows Promise Against Six Viral Infections Common After Stem Cell Transplants. American Association for Cancer Research. January 11, 2022. Accessed on January 11, 2022. AACR.org