CORRELATION OF SPECIFIC IMMUNE-RESPONSES WITH SURVIVAL IN MELANOMA PATIENTS WITH DISTANT METASTASES RECEIVING POLYVALENT MELANOMA CELL VACCINE

Purpose: The mechanisms that underlie the clinical efficacy of melanom a vaccines are not well understood. We hypothesized that the type and strength of the immune response generated by CancerVax (John Wayne Can cer Institute, Santa Monica, CA), a polyvalent melanoma cell vaccine ( PMCV), might be correlated with its effect on overall survival (OS). P atients and Methods: Seventy-seven patients began PMCV therapy after c omplete surgical resection of distant metastatic melanoma. During the first two treatments, PMCV was administered with bacille Calmette-Guer in (BCG). Blood was drawn at 0, 2, 4, 8, and 12 weeks to measure serum titers of immunoglobulin G (IgG) and IgM antibodies against a tumor-a ssociated 90-kd glycoprotein antigen (TA90) expressed on most melanoma cells, including those of PMCV. Cellular immune response to PMCV was assessed by delayed-type hypersensitivity (DTH). General immune compet ence was assessed by skin tests to purified protein derivative (PPD), mumps, and candida. Results: Median follow-up time was 31.5 months. Wi thin the first 12 weeks of PMCV immunotherapy, there was a significant increase in the anti-TA90 IgM (P = .0001) and IgG titers (P = .0001), and in the DTH response to PMCV (P =.0001). Univariate analysis showe d that high anti-TA90 IgM titer and strong PMCV-DTH were associated wi th improved survival (P = .051 and .0173, respectively), whereas eleva ted anti-TA90 IgG was correlated with decreased survival (P = .0119). Multivariate analysis considering clinical variables and PMCV immune r esponses identified anti-TA90 IgM, anti-TA90 IgG, and PMCV-DTH as sign ificant independent variables influencing survival following PMCV immu notherapy (P = .0342, .0105, and .0082, respectively). These responses to PMCV were not correlated with immune responses to BCG and therefor e were not a manifestation of general immune competence for responses to unrelated antigens. The median survival time and 5-year survival ra te were more than 76 months and 75%, respectively, if both anti-TA90 I gM and PMCV-DTH responses were strong (greater than or equal to 800 an d greater than or equal to 7 mm, respectively; n = 29); 32 months and 36%, respectively, if only one response was strong (n = 35); and 19 mo nths and 8%, respectively, if neither was strong (n = 13) (P < .0001). Conclusion: PMCV induces both humoral and cell-mediated immune respon ses to melanoma-associated tumor antigens, the type and strength of wh ich appear to be directly related to its therapeutic efficacy. J Clin Oncol 16:2913-2920. (C) 1998 by American Society of Clinical Oncology.