Tumor stem cell antigens as consolidative active specific immunotherapy: a randomized phase II trial of dendritic cells versus tumor cells in patients with metastatic melanoma.

Only 10% of metastatic melanoma patients survive 5 years, even though many can achieve substantial tumor reduction by surgical resection and/or radiation therapy and/or systemic therapy. An effective, nontoxic, consolidation immunotherapy could benefit such patients. We initiated a randomized trial to compare 2 promising patient-specific immunotherapy cell products. Patients had to have a diagnosis of metastatic melanoma and availability of an autologous melanoma cell line. Patients were stratified by whether their most advanced stage had been regional or distant metastases, and by whether they had measurable disease at the time of treatment, then they were randomized to receive irradiated autologous proliferating tumor cells or autologous dendritic cells (DC) loaded with antigens from such cells. Both products were injected subcutaneously in 500 µg of granulocyte-macrophage colony stimulating factor, weekly for 3 weeks and then monthly for 5 months. Patients in the 2 arms did not differ in baseline characteristics. All patients received prescribed therapy. Treatment was well tolerated. At the time of initial analysis, with no patients lost to follow-up, 50% of patients deceased, and all surviving patients followed for at least 6 months after randomization, survival is superior in the DC arm (hazard ratio, 0.27; 95% confidence interval, 0.098-0.729) with median survival not reached versus 15.9 months, and 2-year survival rates of 72% versus 31% (P=0.007). This trial provides evidence that a DC vaccine is associated with longer survival compared with a tumor cell vaccine, and is consistent with previous data suggesting a survival benefit from this patient-specific immunotherapy.

Lack of elevation of serum S100B in patients with metastatic melanoma as a predictor of outcome after induction with an autologous vaccine of proliferating tumor cells and dendritic cells.

Serum levels of S100B and/or lactate dehydrogenase (LDH) are putative tumor markers in melanoma. Early changes in such markers may correlate with a positive immune response to vaccine therapy. In patients with metastatic melanoma, S100B and LDH serum levels were measured at baseline, and 1 week after 3 weekly subcutaneous injections of investigational, patient-specific vaccines consisting of autologous dendritic cells loaded with antigens from irradiated proliferating autologous tumor cells, and suspended in granulocyte macrophage colony-stimulating factor. There was a poor correlation between S100B and LDH levels at baseline (p = 0.324). Fourteen (14) patients with measurable disease had higher S100B (p = 0.0456) and LDH (p = 0.0013) levels than 31 patients who lacked measurable disease at that time. Fourteen (14) deceased patients (median survival, 13 months) had a mean baseline S100B of 0.62 mug/L (95% confidence interval [CI] 0.00-1.66) and LDH of 815 U/L (95% CI 222-1408); 31 surviving patients (median follow-up, 35.4 months) had mean S100B of 0.07 mug/L (95% CI 0.00-0.23; p = 0.006) and LDH of 442 U/L (95% CI 296-588; p = 0.002). Elevated baseline levels of LDH and S100B were each predictive of inferior progression-free survival (PFS) and overall survival (OS) (both p < 0.0001), but S100B was a better predictor for PFS than LDH. Changes in LDH between baseline and week 4 were not predictive of survival, but an increase in S100B predicted for inferior OS ( p = 0.039). Both LDH and S100B are predictive tumor markers in patients with metastatic melanoma. This is the first study to examine the changes in serum levels of LDH and S100B in response to an autologous tumor-cell vaccine.