Developmental History, Clinical Considerations, and Future Perspectives

Michael A. Postow, MD; Jedd D. Wolchok, MD, PhD


The Melanoma Letter. 2012;30(1):1-4. 

In This Article

Patient Selection: Biomarker Analyses

Considerable efforts have been directed towards understanding immunologic biomarkers associated with disease response to ipilimumab, to help determine which patients might be the best candidates for therapy. Monitoring of immunological parameters of patients undergoing therapy with ipilimumab has therefore been an integral component of completed and ongoing clinical trials. In one retrospective study of 51 patients treated with ipilimumab (10mg/kg), an absolute lymphocyte count (ALC) that exceeded 1000/μL at the time of the third ipilimumab dose (week 7 of therapy) was associated with an overall survival benefit.[8]

Additional work has investigated antigen-specific immune responses to a number of cancer-related antigens. Specifically, immune responses to the cancer-testis antigen NY-ESO-1 before or during ipilimumab therapy have been the most extensively characterized to correlate with clinical activity following therapy. In one recent study of 144 patients, those with detectable serum antibodies to NY-ESO-1 by ELISA prior to or during the course of ipilimumab therapy were more likely to achieve disease control (stable disease or disease response) from ipilimumab than those who did not have the serum antibodies.[9] Seropositive patients treated at Memorial Sloan-Kettering Cancer Center who also had a detectable NY-ESO-1-specific CD8+ T-cell response showed a significant survival advantage compared to seropositive patients without a detectable CD8+ T-cell response. Though immunity to NY-ESO-1 was correlated with clinical benefit from ipilimumab, NY-ESO-1-specific immunity is likely a surrogate marker for the broader mechanisms of ipilimumab's antitumor effects, rather than a direct mediator. Studies of ALC and NY-ESO-1 have identified them as potential biomarkers in retrospective analyses, and prospective validation is an area of active research.


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.
Post as: