Novel T-cell therapy effective against common viruses after stem cell transplantation
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Key findings:
- Posoleucel, an off-the-shelf T-cell therapy, conferred antiviral responses in 95% of patients who underwent allogeneic stem cell transplantation.
- Treatment appeared safe, with no cases of cytokine release syndrome and only four de novo cases of graft-versus-host disease.
Posoleucel demonstrated encouraging efficacy against common viral infections among patients who underwent allogeneic hematopoietic stem cell transplantation, according to phase 2 study results published in Clinical Cancer Research.
The majority (95%) of study participants responded to treatment with posoleucel (Viralym-M, AlloVir), a novel allogeneic T-cell therapy that targets six viral infections that occur after allogeneic HSCT — adenovirus, BK virus, cytomegalovirus (CMV), Epstein-Barr virus, human herpes virus-6 and John Cunningham virus (JCV), researchers noted.
Rationale and methods
Patients who undergo allogeneic HSCT are at high risk for developing potentially life-threatening viral infections in the first 180 days after transplantation, Bilal Omer, MD, pediatric hematologist-oncologist at Texas Children’s Hospital and assistant professor of pediatrics and member of Dan L. Duncan Comprehensive Cancer Center at Baylor College of Medicine, told Healio.
“During the past 2 decades, a handful of academic centers have demonstrated that virus-specific T-cell therapies could be used to successfully treat these infections in individual patients. However, these cells had to be individually generated for each patient, and the required time for manufacture limited the potential for broad adoption,” Omer said. “More recent advances have made it possible to develop a new generation of virus-specific T-cell therapies that can be developed prospectively for off-the-shelf delivery to patients. One of them, posoleucel, has the ability to target multiple viruses at once.”
Omer and colleagues assessed the safety and efficacy of posoleucel against the six viruses it targets among 58 children and adults who underwent allogeneic HSCT for the treatment of cancer or other blood diseases.
All patients could not tolerate or did not respond to prior standard treatments for the viruses. Of the 70 viral infections included in the study population, CMV and BK virus occurred most often.
Researchers defined complete response to posoleucel as reduction of viral load to normal range with resolution of clinical signs and symptoms and partial response as viral load reduction of at least 50% or a 50% improvement in clinical signs and symptoms.
Results
Researchers reported an overall response rate of 95% (95% CI, 85.6-98.9) within 6 weeks of the first infusion of posoleucel, as well as a 97% reduction in median plasma viral load.
All but one of the 46 patients with a single virus infection experienced either a partial or complete response by week 6. Of the 12 patients with more than one viral infection, 10 (83%) achieved either a partial or complete response.
Results specifically showed treatment responses in 83% of patients with adenovirus (n = 12), among all patients with BK virus (n = 27), in 96% of patients with CMV (n = 24) and in all patients with Epstein-Barr virus (n = 2).
Further, three out of the four patients with human herpes virus 6 responded to treatment and all four patients experienced viral load reduction. One patient with JCV initially experienced stabilized disease, but later progressed and died.
No patients experienced cytokine release syndrome. Although 22% of patients reported acute graft-versus-host disease, only four patients had de novo cases, as nine had a GVHD diagnosis before the study.
A limitation of the study included the single-arm design, researchers noted.
Looking ahead
“The safety and efficacy profile of posoleucel support the initiation of two phase 3 — one for the treatment of virus-associated hemorrhagic cystitis that is most often caused by BK virus, and one for the treatment of adenovirus infection in allogeneic HSCT patients,” Omer told Healio. “There are no effective treatments for either of these viral infections and diseases, which have significant morbidity and mortality. There is an important need to bring therapies forward for these patients.”
Posoleucel is also being examined as preventive therapy, Omer added.
“This prevention approach would be transformational for the allogeneic HSCT field, helping to reduce or eliminate a significant risk to patient outcomes post-transplant,” he said.
References:
- Pfeiffer T, et al. Clin Cancer Res. 2023;doi:10.1158/1078-0432.CCR-22-2415.
- An investigational T-cell therapy shows promise against six viral infections common after stem cell transplants (press release). Available at: www.aacr.org/about-the-aacr/newsroom/news-releases/an-investigational-t-cell-therapy-shows-promise-against-six-viral-infections-common-after-stem-cell-transplants/. Published Jan. 11, 2023. Accessed Jan. 11, 2023.
For more information:
Bilal Omer, MD, can be reached at bomer@bcm.edu.
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