Combining chemotherapy and autologous peptide-pulsed dendritic cells provides survival benefit in stage IV melanoma patients

Abstract

Background and objectives: We examined retrospectively whether the combination of standard dacarbazine (DTIC) and/or fotemustine chemotherapy and autologous peptide-loaded dendritic cell (DC) vaccination may improve survival of stage IV melanoma patients. Furthermore, a small cohort of long-term survivors was studied in more detail.

Patients and methods: Between 1998 and 2008, 41 patients were vaccinated at least three times with DCs while receiving chemotherapy and compared to all other 168 patients in our database who only received chemotherapy (1993-2008).

Results: Median life expectancy of patients receiving additional DC-vaccination was 18 months, compared to eleven months for patients under standard chemotherapy alone. In contrast to patients with other haplotypes, the HLA-A1/A1 subset of DC-treated patients showed significantly lower median survival (12 vs. 25 months). Autoantibodies were frequently detected in serum of both vaccinated and non-vaccinated patients, and there was no correlation between titers, loss or appearance of autoantibodies and survival. Additionally, phenotyping of DCs and PBMCs also did not reveal any conspicuous correlation with survival.

Conclusions: Combining standard chemotherapy and DC vaccination appears superior to chemotherapy alone. The impact of HLA haplotypes on survival emphasizes the importance of a careful selection of patients with specific, well-defined HLA haplotypes for future vaccination trials using peptide-pulsed DCs, possibly combined with checkpoint inhibitors.

Figure 1

Kaplan‐Meier curves of overall survival by treatment arm. Arm A (in green: standard chemotherapy with DTIC and/or fotemustine), 168 patients and 136 deaths; arm B (in blue: standard chemotherapy plus DC vaccination), 41 patients and 31 deaths. P = 0.01 by log rank test. Censored observations are indicated by vertical bars.

Figure 2

Kaplan‐Meier curves of overall survival of additionally DC‐vaccinated patients (group 1) by HLA haplotype. Arm A (in green: HLA‐A1/A1 haplotype), 12 patients and 12 deaths; arm B (in blue: all other HLA haplotypes), 29 patients and 19 deaths. P = 0.015 by log rank test. Censored observations are indicated by vertical bars.

Figure 3

Kaplan‐Meier curves of overall survival by the presence of autoantibodies. Arm A (in green: patients with autoantibodies at second measurement), 22 patients and 15 deaths; arm B (in blue: patients without autoantibodies at second measurement), 24 patients and 20 deaths. P = 0.67 by log rank test. Censored observations are indicated by vertical bars.