Assessing Response of High-grade Gliomas to Immune Checkpoint Inhibitors

Solmaz Sahebjam, MD; Dexter G. Stallworth, MD; Sepideh Mokhtari, MD; Nam D. Tran, MD, PhD; John A. Arrington, MD

Disclosures

Cancer Control. 2017;24(2):180-186. 

In This Article

Abstract and Introduction

Abstract

Background. Immunotherapeutic agents, especially checkpoint inhibitors, have emerged as the mainstay of therapy for several solid and hematological malignancies. These therapies are under investigation for the treatment of high-grade gliomas and brain metastases.

Methods. This article reviews the unique challenges encountered when evaluating changes on magnetic resonance imaging (MRI) of glioblastomas seen in response to immunotherapy and checkpoint inhibitors and how to effectively incorporate MRI findings into the response assessment of high-grade gliomas to these emerging therapies.

Results. An increase in tumor size or the appearance of new lesions on MRI may represent either an immune-mediated inflammatory response or true tumor progression, which may precede the subsequent stabilization or response of high-grade gliomas to immunotherapy. These MRI findings should not result in the mandatory cessation of immunotherapy in patients with high-grade glioma.

Conclusions. Although immunotherapy Response Assessment for Neuro-Oncology criteria have been developed to assist with response assessment of high-grade gliomas to immunotherapy and to provide guidance with treatment decisions, these criteria have not been validated in prospective clinical trials. In patients with brain tumors who are receiving immunotherapy, MRI findings suggestive of disease progression should be evaluated with caution to prevent premature discontinuation of potentially beneficial therapies. Close, clinical monitoring with appropriate short-term, follow-up imaging is often necessary, and histopathological analysis may be required in some cases to confirm disease progression before a decision on continuation of these novel therapies can accurately be made.

Introduction

Immune checkpoint inhibitors have emerged as a mainstay of treatment for a variety of advanced malignancies. Antibodies against cytotoxic T-lymphocyteassociated protein 4, programmed death 1 (PD-1), and its ligand (PD-L1) have demonstrated significant clinical benefit in several solid and hematological malignancies, and their list of approved indications is expanding.

Anti–PD-1/PD-L1 antibodies alone or in combination with ipilimumab, an anti–cytotoxic T-lymphocyte-associated protein 4 antibody, is being investigated in patients with high-grade gliomas.[1–3] These therapies are well tolerated in patients with newly diagnosed or recurrent glioblastoma (GBM).[1–3] Although the clinical benefit of these antibodies in the setting of high-grade glioma is yet to be confirmed, the preliminary data from small cohorts suggest an antitumor effect and clinical benefit when these agents are used as single-agent or combination therapy.[1,3,4]

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