According to the researchers, posoleucel appears safe and effective for treating refractory viral infections that occur after allogeneic hematopoietic stem cell transplantation (allo-HSCT).
Posoleucel is a ready-to-use virus-specific T-cell product designed to treat or prevent multiple viral infections commonly seen in the allo-HSCT setting.
The investigators found that posoleucel caused either a complete response (CR) or a partial response (PR) in nearly all treated patients. These results were published in Clinical Cancer Research.
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Results are from the phase 2 CHARMS trial (ClinicalTrials.gov Identifier: NCT02108522). The trial included 58 patients who had received allo-HSCT and had a viral infection that was unresponsive or 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 was a total of 70 infections treated. 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 (one %).
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 of receiving a second infusion at 4 weeks followed by bi-weekly infusions thereafter. Most patients (67%) received a single infusion, 26% received 2 infusions, and 7% received 3.
The primary efficacy outcome was the 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 CR and 12 PR) and 83% for patients with adenovirus (6 CR and 4 PR). Responses were observed in all evaluable patients with human herpes virus 6 (3 PR), Epstein-Barr virus (2 PR), or BK virus (27 PR).
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-versus-host disease (GVHD): 10 patients with Grade 1 GHVD, 2 with Grade 2 GVHD, and 1 with Grade 1 GVHD. 3. Three of these patients had active GVHD at study entry, 6 had inactive GVHD at study entry, and 4 had no history of GVHD. Most cases of GVHD resolved (n=8) or improved (n=4) at week 6.
There were no cases of cytokine release syndrome or other infusion-related adverse events.
“[R]The results of our trial suggest that posoleucel is a safe and effective therapy for the treatment of severe viral infections after allogeneic HCT,” the researchers concluded. “Their use could help alleviate the morbidity and mortality associated with post-HCT viral infections and help avoid the nephrotoxic and myelosuppressive side effects associated with the use of conventional antiviral drugs.”
Disclosures: This research was supported by AlloVir. Some study authors declared affiliations with biotechnology, pharmaceutical, and/or device companies. Please see the original reference for a complete list of disclosures.
Reference
Pfeiffer T, Tzannou I, Wu M, 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. Published online January 11, 2023. doi:10.1158/1078-0432.CCR-22-2415
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