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Active Immunotherapy by Reinduction With a Polyvalent Allogeneic Cell Vaccine Correlates With Improved Survival in Recurrent Metastatic Melanoma

From the Sonya Valley Ghidossi Vaccine Laboratory of the Roy E. Coats Research Laboratories of the John Wayne Cancer Institute, St. John’s Health Center, Santa Monica, California.

Correspondence: Address correspondence and reprint requests to: Eddy C. Hsueh, MD, John Wayne Cancer Institute, 2200 Santa Monica Blvd., Santa Monica, CA 90404; Fax: 310-449-5261; E-mail: hsuehe{at}jwci.org

Background: We have observed prolonged survival in patients undergoing vaccine reinduction after resection of recurrent metastatic melanoma and adjuvant polyvalent allogenic cell vaccine (PACV) immunotherapy. We hypothesized that reinduction with a more intensive vaccine regimen would re-stimulate specific immune responses that were correlated with survival after recurrence.

Methods: From 1996 to 1998, 194 patients developed recurrence during adjuvant PACV (CancerVax vaccine) treatment after resection of metastatic melanoma. Recurrent disease was treated with or without vaccine reinduction. Reinduction regimen entailed an increased vaccine frequency and coadministration of two doses of bacille Calmette-Guérin (BCG). PACV Delayed-type hypersensitivity (DTH) responses were prospectively recorded. Survival was defined as the interval from recurrence to death.

Results: Ninety-four patients underwent reinduction immunotherapy. DTH responses to PACV before recurrence increased significantly after reinduction therapy (P = .0001). The median survival time was 37 months for reinduced patients and 17 months for other patients. On multivariate analysis, reinduction status remained a significant prognostic variable (P = .0277). In the reinduction group, there was a significant correlation between PACV DTH responses and survival (P = .0178).

Conclusions: Reinduction vaccine regimen can enhance immune responses in previously immunized patients and is associated with prolonged survival after recurrence in patients receiving the same active specific immunotherapy.

Key Words: Melanoma • Immunotherapy • Reinduction • Tolerance

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