Posoleucel appears safe and effective for treating refractory viral infections occurring after allogeneic hematopoietic stem cell transplant (allo-HSCT), according to researchers.
Posoleucel is an off-the-shelf virus-specific T-cell product designed to treat or prevent multiple viral infections that are frequently observed in the allo-HSCT setting.
Researchers found that posoleucel elicited a complete response (CR) or partial response (PR) in nearly all treated patients. These results were published in Clinical Cancer Research.
The results come from the phase 2 CHARMS trial (ClinicalTrials.gov Identifier: NCT02108522). The trial included 58 patients who had received allo-HSCT and had an unresponsive viral infection or were intolerant to standard antiviral therapies. The cohort included adult (69%) and pediatric (31%) patients. About half (52%) were men or boys, and 88% were White.
Patients were receiving allo-HSCT for acute myeloid leukemia or myelodysplastic syndromes (41%), acute lymphoblastic leukemia or mixed-phenotype acute leukemia (29%), nonmalignant disease (21%), and lymphoma, multiple myeloma, or chronic myeloid leukemia (9%).
There were a total of 70 treated infections. Forty-six patients were treated for a single infection, 11 were treated for 2 infections, and 1 patient was treated for 3 infections. Infections included BK virus (39%), cytomegalovirus (34%), adenovirus (16%), human herpes virus 6 ( 6%), Epstein-Barr virus (3%), and JC virus (1%).
One patient was enrolled in the study twice, once for adenovirus and once for JC virus. This patient was counted twice in the efficacy analysis but once in the safety analysis.
Posoleucel was administered as a single infusion (2 x 107/m2), with the option to receive a second infusion at 4 weeks followed by biweekly infusions thereafter. Most patients (67%) received a single infusion, 26% received 2 infusions, and 7% received 3.
The primary efficacy outcome was antiviral response at 6 weeks after the first dose. At that time, the overall response rate (ORR) was 95%. The ORR was 98% for patients with a single infection and 83% for patients with multiple infections.
The ORR was 96% for patients with cytomegalovirus (11 CRs and 12 PRs) and 83% for patients with adenovirus (6 CRs and 4 PRs). Responses were seen in all evaluable patients with human herpes virus 6 (3 PRs), Epstein-Barr virus (2 PRs), or BK virus (27 PRs).
The patient who was treated for JC virus achieved an initial response to posoleucel but ultimately died of progressive multifocal leukoencephalopathy.
By week 6, 13 patients (22%) had developed acute graft-vs-host disease (GVHD) — 10 patients with grade 1 GHVD, 2 with grade 2, and 1 with grade 3 GVHD. Three of these patients had active GVHD at study entry, 6 had quiescent GVHD at study entry, and 4 had no history of GVHD. Most GVHD cases had resolved (n=8) or improved (n=4) by week 6.
There were no cases of cytokine release syndrome or other infusion-related adverse events.
“[R]esults of our trial suggest that posoleucel is a safe and effective therapy for the treatment of severe viral infections following allogeneic HCT,” the researchers concluded. “Its use might aid in alleviating the morbidity and mortality associated with post-HCT viral infections and helps avoid the nephrotoxic and myelosuppressive side effects associated with the use of conventional antiviral medications.”
Disclosures: This research was supported by AlloVir. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Pfeiffer T, Tzannou I, Wu M, 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.Clin Cancer Res. Published online January 11, 2023. doi:10.1158/1078-0432.CCR-22-2415