妖姬直播

Intratumoral infusion of an oncolytic virus offered safe and feasible results, along with encouraging efficacy, in pediatric patients with diffuse intrinsic pontine glioma (DIPG), researchers reported.

In the phase I study of 12 pediatric patients with DIPG, infusion of oncolytic virus , followed by radiotherapy (RT) in all but one patient, resulted in a median overall survival (OS) of 17.8 months, with an OS rate at 18 months of 50%, according to Marta Alonso, PhD, of Universidad de Navarra in Pamplona, Spain, and colleagues.

Nine patients lived more than a year after the administration of DNX-2401, while three lived longer than 2 years. The patient who did not receive radiotherapy survived 13.4 months after DNX-2401 administration, they stated in the (NEJM).

At data cutoff, three patients remained alive at 19.6, 31.4, and 33.5 months after DNX-2401 administration, while two patients were still alive at the time the NEJM paper was prepared, including a patient who was free of tumor progression at 38 months, according to the authors.

However, "the small sample size in our study and the lack of a randomized design preclude any conclusion regarding survival," Alonso's group cautioned. "There is preclinical evidence of direct oncolytic activity of our treatment model and suggestive evidence that this model was operative in our patients, but we have limited information to address the relative contributions of the change in inflammatory response in the tumor and viral oncolytic activity."

They reported that, over a median follow-up of 17.8 months, there was a reduction in tumor size on MRI reported in nine patients, a partial response in three patients, and stable disease in eight patients. In addition, an examination of a tumor sample obtained from one patient on autopsy, as well as peripheral-blood studies, "revealed alteration of the tumor microenvironment and T-cell repertoire," Alonso and colleagues stated.

The prognosis of children with DIPG is bleak, involving severe neurologic morbidity and poor OS. Previous involving patients with DIPG treated with RT alone demonstrated median OS of 8 to 12 months, with little additional benefit observed with various drugs such as , everolimus, dasatinib (Sprycel), or erlotinib (Tarceva).

The authors noted that while oncolytic viral therapy has been evaluated in patients with pediatric gliomas elsewhere in the brain, data for this kind of therapy in patients with DIPG are lacking, "owing to the difficulty of reaching the location of the brain-stem tumor and the concern over procedure-associated complications and virotherapy-related inflammation in the pons."

The current results "suggest that intratumoral infusion of DNX-2401 before radiation therapy is feasible in children with DIPG, providing a rationale for the conduct of a larger trial," they wrote.

Median patient age in the study was 9 years, and more than half were female. They had newly diagnosed DIPG, confirmed on the basis of clinical and MRI features of an infiltrating tumor involving at least 50% of the pons, and had a Lansky or Karnofsky performance-status score of 70 or higher.

After undergoing a biopsy procedure, patients received a single virus infusion through a catheter placed in the cerebella peduncle. Successful delivery of the virus was confirmed with MRI.

Postoperatively, patients received standard-of-care RT. When there was tumor progression, patients received further treatment -- including chemotherapy, re-irradiation, antiangiogenic therapy, or investigational agents -- at the discretion of their oncologist. One patient underwent a second intratumoral infusion of DNX2401 through compassionate use.

Regarding safety, the most frequent adverse events (AEs) were headache, neurologic deterioration, and vomiting in nine patients each, fatigue in eight patients, and fever in six patients. Most were low-grade, with only one grade 3 event.

Three serious AEs were reported, but no grade 4 or 5 AEs. Nine patients had at least one AE that was deemed to be possibly related to intratumoral delivery of DNX-2401.

In an , Evanthia Galanis, MD, of the Mayo Clinic in Rochester, Minnesota, noted that this study, along with two previous NEJM studies, demonstrated evidence of biologic activity in patients with gliomas, "generating a glimmer of hope for patients and their families afflicted by these diseases." The 2018 and 2021 studies used different oncolytic virus platforms.

"Expanded testing in phase 2 trials of these three and used in the treatment of brain tumors is planned or ongoing," wrote Galanis. "These studies provide important opportunities for correlative analyses that can help us understand how to enrich future trials with patients who have the highest likelihood of benefitting from oncolytic immunovirotherapy and how to match patients with the appropriate virus or viruses for their disease. Proceeding to the conduct of large, randomized trials without careful, data-driven patient selection reduces the likelihood of success."

Comment