I reviewed with great interest the recent article on the AACR’s 2013 Cancer Progress Report highlighting advances in immunotherapy (OT, 10/25/13 issue). As a clinician who closely follows this area of research, I share the AACR’s concern about the current oncology research funding crisis, and I echo AACR’s call for greater patient participation in cancer clinical trials. Such participation is crucial to the continued advancement and adoption of immunotherapy, a treatment modality that has been shown to produce meaningful and durable responses in a subset of patients, and which is “beginning to revolutionize the treatment of certain cancers,” in the words of AACR President Charles L. Sawyers, MD.
Whereas immunotherapeutic agents such as ipilimumab and interleukin-2 (IL-2) are thought to modulate “natural immunity,” the nature of their clinical effector process is not well understood. When we have therapies capable of durable response but such benefits are limited to a select group of patients, greater effort needs to be applied to identifying the predictive and prognostic markers of response. Understanding such biomarkers will enhance response rates (i.e., by enabling selection of appropriate patients) and limit toxicity (i.e., by facilitating appropriate dosing). In addition, biomarker studies tied to clinical trials will provide a basis for rational combinations.
Registration databases have been established for ipilimumab and IL-2, and clinical trials such as the ongoing PROCLIVITY program are advancing understanding of combination immunotherapy. However, the lack of significant funding outside of industry has limited understanding of biomarkers. While the registration databases are collecting valuable clinical information, they lack annotated tissue samples needed for biomarker studies. Ideally, every patient undergoing immunotherapy should receive immunologic assessments just as they have CT scans and other blood tests. Yet we lack the basic understanding that would allow immunologic assessments. Consequently, we are administering costly therapies to patients who may only experience toxicity.
Policymakers should increase support for translational research focused on understanding the expanding number of tools available to the treating clinician. One such tool is the immune score, a proposed classification system that quantifies the density and location of immune cells within a tumor, and which purportedly has a prognostic value exceeding that of the AJCC/UICC TNM-classification.1 The immune score is emblematic of the huge strides we have made in translational research, and may eventually be regarded as the immunotherapeutic equivalent of molecular targeting, which has led the way to personalized cancer care. Indeed, enhanced understanding of these potentially valuable tools may someday lead us to the era of personalized immunotherapy.
Gregory A. Daniels, MD, PhD
Moores UCSD Cancer Center
La Jolla, CA
1. Galon J, Pages F, Marincola FM, et al. The immune score as a new possible approach for the classification of cancer. J Transl Med. 2012;10:1. http://www.translational-medicine.com/content/10/1/1