Dendritic cell vaccination in melanoma patients: Update and subgroup analysis of clinical response to post-vaccine treatment

Abstract

9042 Background: Dendritic cells (DCs) play a crucial role in the interplay between innate and adaptive immune response towards cancer. The combination of immunotherapies with standard treatments for cancer could represent a further chance for advanced melanoma patients. In the literature, higher response rates than those normally obtained have been reported after second-line chemotherapy in patients with non small cell lung cancer pre-treated with vaccines and in patients with follicular B-cell lymphoma vaccinated with an anti-idiotype vaccine whilst in remission. On the basis of this data, we reviewed and updated the clinical results of our dendritic cell based vaccine clinical trial in stage IV melanoma patients. Methods: From December 2002 to 2007, 24 pre-treated metastatic melanoma patients were vaccinated with mature DCs (mDCs) pulsed with autologous tumor lysate (ATL) and keyhole limpet hemocyanin (KLH) followed by a 5-day treatment with low-dose subcutaneous Interleukin-2. Results: We observed 2 complete response (CR), 2 mixed response (MR), 5 partial response (PR), 4 stable disease (SD) and 11 progressive disease (PD) (overall response (OS) 37.5%; clinical benefit 54.1%). All 13 responders had delayed-type hypersensitivity (DTH) positivity to KLH, of whom 10 also showed positivity to the lysate. Eleven (45.8%) of the 24 patients underwent further lines of treatment (5 chemotherapy [CT], 3 surgery [S], 4 biotherapy, 2 radiotherapy [RT] and 4 biochemotherapy [BioCT]) after stopping vaccination (8 due to progression and 3, in SD, because all of their lysate had been used). Of these 11 patients, 2 obtained CR (1 RT, 1 S), 5 PR (3 BioCT, 2 S) for an OR of 63.6%, 1 SD (BioCT) and 3 showed PD as the best response to subsequent therapies, with a median OS of 30 months (range 16–52). Of the 3 SD patients who were forced to stop vaccine treatment, 1 had CR following RT and 2 progressed. Conclusions: Metastatic melanoma responds poorly to standard therapy, in particular after first-line treatment. Vaccination could enhance clinical response to subsequent third- or fourth-line therapies, thus prolonging overall survival. No significant financial relationships to disclose.