Studies show that viral infections are common causes of morbidity and mortality in patients undergoing hematopoietic stem cell transplantation and can induce a profound immunocompromised state in some patients that may last up to 24 months or longer posttransplant. In an open-label, single-arm, phase III study investigating the feasibility and safety of posoleucel, an allogeneic, off-the-shelf multivirus-specific T-cell therapy that targets six common viruses, results showed the therapy demonstrated promising antiviral efficacy and safety in 95% of patients who had undergone stem cell transplantation for the treatment of blood cancers or other blood diseases. Posoleucel, formerly known as ALVR105,  is now being evaluated in three randomized phase III clinical trials for both treatment and preventive indications. The study by Pfeiffer at al was published in Clinical Cancer Research.

Study Methodology

The researchers enrolled 58 adult and pediatric patients who had undergone an allogeneic hematopoietic cell transplant and were infected with one or more of the six viral infections that commonly occur in allogeneic stem cell transplantation recipients. The six viruses included: adenovirus, BK virus (BKV), cytomegalovirus (CMV), Epstein-Barr virus, human herpes virus–6, and JC virus.

Eligible patients were either unresponsive to or unable to tolerate standard therapies for these viruses. In total, there were 70 viral infections in this patient population, the majority of which were CMV and BKV.

Results

The study found that posoleucel was well tolerated, with no cytokine-release syndrome or other infusion-related toxicities; two patients (3.4%) developed grade 2 graft-vs-host disease and one patient (1.7%) developed grade 3 graft-vs-host disease during the trial. The overall response rate 6 weeks after the first posoleucel infusion was 95%, with a median plasma viral load reduction of 97%. Of the 12 patients who had two or more target viral infections identified at study enrollment, 10 (83%) had a clinical response for all evaluable viruses. Of the 23 patients treated for refractory BKV-associated hemorrhagic cystitis, 74% had resolution of symptoms and macroscopic hematuria by 6 weeks postinfusion.

Responses were defined as a reduction of viral load to normal range with resolution of clinical signs and symptoms (complete response), or as a viral load reduction of at least 50% or a 50% improvement of clinical signs and symptoms (partial response).

“In this open-label trial, treatment of refractory viral infections/disease in allogeneic hematopoietic cell transplant recipients with posoleucel was feasible, safe, and effective,” concluded the study authors.

Translational Relevance

“The key finding is that 95% of patients whose infections had been refractory to conventional therapies responded to posoleucel with corresponding reductions in viral load and with limited rates of graft-vs-host disease,” said Thomas Pfeiffer, MD, Assistant Professor of Pediatrics at Washington University School of Medicine in St. Louis, Missouri, and first author of the study, in a statement. “Overall, posoleucel was found to be very effective and had a favorable safety profile in a highly vulnerable patient population.”

Dr. Pfeiffer, of Washington University School of Medicine in St. Louis, and Bilal Omer, MD, of the Dan L. Duncan Comprehensive Cancer Center at Baylor College of Medicine, are the corresponding authors of this study.

Disclosure: Funding for this study was provided by the National Heart, Lung, and Blood Institute Production Assistance for Cellular Therapies; Conquer Cancer Foundation/ASCO; Dan L. Duncan Comprehensive Cancer Center; and the National Institutes of Health. For full disclosures of the study authors, visit aacrjournals.org/clincancerres.