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Molecular Tumor Markers in the Blood: Early Prediction of Disease Outcome in Melanoma Patients Treated With a Melanoma Vaccine

Robert A. Wascher, Donald L. Morton, Christine Kuo, Robert M. Elashoff, He-Jing Wang, Mehri Gerami, Dave S.B. Hoon

From the Department of Molecular Oncology, John Wayne Cancer Institute, Saint John’s Health Center, Santa Monica; and Department of Biomathematics, University of California Los Angeles School of Medicine, Los Angeles, CA.

Address reprint requests to Dave S.B. Hoon, PhD, Department of Molecular Oncology, John Wayne Cancer Institute, 2200 Santa Monica Blvd, Santa Monica, CA 90404; email: hoond{at}jwci.org.

Purpose: Patients with American Joint Committee on Cancer (AJCC) stage III melanoma are at high risk of recurrence and death. We hypothesized that a multiple-marker reverse transcriptase polymerase chain reaction (MM-RT-PCR) blood assay could predict, early in the course of therapy, those patients destined to experience treatment failure with a melanoma vaccine (MV) previously shown to improve survival in a phase II clinical trial.

Patients and Methods: After complete surgical resection, prospectively collected cryopreserved peripheral-blood lymphocyte specimens (n = 90) from the serial bleeds of 30 patients with AJCC stage III melanoma were studied by MM-RT-PCR, using the markers tyrosinase, melanoma antigen recognized by T cells-1 (MART-1), and universal melanoma antigen gene-A (uMAG-A). All patients were enrolled in a phase II MV trial during the period of blood draws, and were selected for this study in a blinded fashion. Median duration of clinical follow-up was 74 months for the 13 survivors and 11 months for the 17 nonsurvivors.

Results: The presence of at least one melanoma-specific RT-PCR marker was associated with an increased risk of disease recurrence (risk rate, 3.12; P = .02) and decreased risk of survival (relative rate, 2.62; P = .0496) by multivariate analysis.

Conclusion: MM-RT-PCR of the blood provided early prediction of subsequent disease recurrence and death in clinically disease-free AJCC stage III melanoma patients enrolled in a MV phase II trial. On the basis of the results of this pilot study, the MM-RT-PCR blood assay should be considered as a clinically important monitoring tool for assessing patient response to adjuvant therapy, and in the surveillance of clinically disease-free patients for the earliest signs of recurrence.

Supported in part by National Institutes of Health, National Cancer Institute P01 Grants CA 29,605 and CA 12,528, Project II.

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