An investigational ready-to-use T-cell therapy appears to be effective against six different viral infections that are common in patients undergoing allogeneic hematopoietic cell transplantation (HCT), according to the results of a phase II trial.
Posoleucel achieved a partial or complete antiviral response in 95% of 58 adult and pediatric patients infected with one or more of the viruses within 6 weeks of the first infusion with the targeted multiviral therapy, reported Bilal Omer, MD, of Baylor College. of Medicine in Houston, and colleagues at Clinical Cancer Research.
“The response rate was quite high, and this is remarkable because these patients, for the most part, either did not tolerate conventional therapies or had failed conventional therapies altogether. So these were patients with quite significant viral infections,” Omer said. . Med Page Today. “And we were able to treat these patients quickly, within 24 to 48 hours, with this ready-to-use product.”
“These infections are quite a significant problem, and while we have made progress with other types of infections, there just aren’t many effective and safe medications for virus infections,” Omer continued. “And these patients can get quite serious viral infections, usually in the first 3 to 6 months after transplant, which are the cause of both morbidity and mortality.”
Omer explained that some centers have treated these patients using donor-derived virus-specific T cells. And while effective, “these need to be generated individually for each of these patients, they cost a lot of money and take time to make,” limiting the widespread adoption of this approach.
In this case, Omer and colleagues used standard T cells that were generated from healthy donors to attack six viral viral pathogens in immunocompromised patients: adenovirus, BK virus, cytomegalovirus, Epstein-Barr virus, human herpes virus-6 ( HHV -6), and JC virus.
Of the 58 patients treated, approximately half were male (52%) and 18 (31%) were under the age of 18 at enrollment. Transplant donor sources included matched unrelated (48%), cord blood (16%), mismatched unrelated (16%), haploidentical (10%), and matched relatives (10%).
Of the 70 evaluable infections treated, the majority were caused by BK virus (39%) or cytomegalovirus (34%), the researchers reported. The vast majority, 46 of the patients, had a single virus at enrollment, while 12 had two or more of the target viruses.
The investigators found that by 6 weeks after the initial posoleucel infusion, partial or complete antiviral responses were achieved in 55 of the entire cohort of 58 patients: 45 of 46 with one virus infection and 10 of 12 patients with two or more. patients. virus
Regarding specific viruses, antiviral responses were achieved in 10 of 12 adenovirus patients, all 27 BK virus patients, 23 of 24 cytomegalovirus patients, both Epstein-Barr virus patients, and three of four HHV-6 patients. , with viral virus. reduced burden on the other patient as well.
The only patient with JC virus had initial stabilization of viral symptoms, which then, however, eventually progressed and the patient died.
Omer explained that considering that the patients received T cells from donors with different human leukocyte antigen types than individual patients, one of the main safety concerns was graft-versus-host-disease (GVHD), which was reported in 13 patients during the trial: grade 2 in two patients and grade 3 in one patient.
“We really didn’t see any severe GVHD,” he said. “We did see a couple of patients who had rashes, and they were transient, they were signs of grade 1 cutaneous GVHD, but they were mostly mild and self-limiting, and we didn’t see any indication that this product would cause moderate or severe GVHD.”
No cases of cytokine release syndrome or other infusion-related toxicities were reported.
The researchers noted that posoleucel is currently being evaluated in three randomized phase III trials for treatment and prevention indications.
![Author['full_name']](https://clf1.medpagetoday.com/media/images/author/MikeBassett_188.jpg)
Mike Bassett is a staff writer specializing in oncology and hematology. He is based in Massachusetts.
Disclosures
The trial was sponsored by AlloVir.
Omer reported the AlloVir research funding; several co-authors reported relationships with industry.
main source
clinical cancer research
Source Reference: Pfeiffer T, et al “Posoleucel, a ready-to-use, allogeneic, multivirus-specific T-cell therapy for the treatment of refractory viral infections in the post-HCT setting” Clin Cancer Res 2023; DOI:10.1158/1078-0432.CCR-22-2415.
Source: news.google.com