The Safety of available immunotherapy for the treatment of glioblastoma

ABSTRACT

Introduction: Glioblastoma (GBM) is the most common malignant primary brain tumor in adults. Current standard of care involves maximal surgical resection combined with adjuvant chemoradiation. Growing support exists for a role of immunotherapy in treating these tumors with the goal of targeted cytotoxicity. Here we review data on the safety for current immunotherapies being tested in GBM.

Areas covered: Safety data from published clinical trials, including ongoing clinical trials were reviewed. Immunotherapeutic classes currently under investigation in GBM include various vaccination strategies, adoptive T cell immunotherapy, immune checkpoint blockade, monoclonal antibodies, and cytokine therapies. Trials include children, adolescents, and adults with either primary or recurrent GBM.

Expert opinion: Based on the reviewed clinical trials, the current immunotherapies targeting GBM are safe and well-tolerated with minimal toxicities which should be noted. However, the gains in patient survival have been modest. A safe and well-tolerated combinatory immunotherapeutic approach may be essential for optimal efficacy towards GBM.

KEYWORDS:

• Glioblastoma
• immunotherapy
• clinical trials
• safety
• adverse events

Article highlights

• Various immunotherapeutic platforms are currently in clinical testing including various peptide, dendritic cell, and heat shock protein vaccination strategies, adoptive T-cell transfer, checkpoint blockade, monoclonal antibodies, and cytokine therapies.

• As these platforms begin to show promise with regard to efficacy, safety is a chief concern as well.

• Safety concerns include autoimmune reactions, on-target vs. off-target toxicity, tumor lysis syndrome, cytokine storming, dosing thresholds, and route of administration.

• Peptide vaccine therapy is currently the furthest along in clinical testing with minor systemic adverse reactions such as injection-site erythema, muscle pain, headache and fatigue.

• Overall, based on current clinical trial data, immunotherapies targeting GBM are safe and well-tolerated with minimal toxicities and should continue to be studied.

• Combining active immunotherapeutic modalities will be key for future therapies to maintain robust clinical responses while minimizing safety concerns.

This box summarizes key points contained in the article.

Declaration of interest

J Sampson has acted as a consultant/advisory role and received research funding from Celldex Therapeutics. He also receives funding under the Duke University Faculty Plan from license fees paid to Duke University from Celldex Therapeutics. Duke University also has the potential to receive patent-related royalties.

Additional information

Funding

This paper was not funded.