Dr Fecci on Immunotherapy Research Innovations in Glioblastoma

“There’s a lot of work being done out there to understand mechanistically how the immune system fails in patients with glioblastoma and other cancers. It’s important to gain that knowledge…because we can use that knowledge then to redesign the therapies and start to see signals.”

Peter E. Fecci, MD, PhD, a professor and chair of the Department of Neurosurgery at the University of Colorado Anschutz, discussed recent therapeutic advances and ongoing challenges in the management of glioblastoma, and overviewed the broader glioma landscape, emphasizing the trajectory of immunotherapy development.

Fecci began by noting the importance of the IDH inhibitor class, including vorasidenib (Voranigo). These agents have produced a recognizable efficacy signal in clinical trials for patients with lower-grade gliomas harboring IDH mutations, he stated. Although this population is distinct from glioblastoma, Fecci contextualized that glioblastoma belongs to the larger glioma category, which encompasses varying histologies. He characterized the emergence of IDH inhibition as a relatively potent advance for the field overall.

Turning to what remains to be developed in the pipeline, Fecci focused on immunotherapy. He emphasized that the glioblastoma field has accumulated substantial knowledge regarding why immunotherapies fail in patients, largely because of the quanity of attempts at evaluating these types of therapies. Investigators are now conducting deeper mechanistic interrogations of those failures, which Fecci noted could help address underlying issues and lead to more solutions and successes. Considerable work is underway to understand mechanistically how the immune system fails in patients with glioblastoma and other malignancies, he noted, with the goal of applying that knowledge to redesign therapies and generate meaningful efficacy signals.

Fecci also highlighted the characteristic all-or-none behavior of immunotherapy, which works dramatically well for some patients and not at all for others. Paradoxically, he emphasized, this dichotomy creates opportunity: because the difference between profound responders and nonresponders is often noticeable, it becomes tractable to study. Identifying the predictors underlying that divergence, then capitalizing on them, represents a key path forward for this field of research, Fecci concluded.