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

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Author(s): L. Ridolfi,
L. Fiammenghi, M. Petrini, A. M. Granato, V. Ancarani, E. Pancisi, L.
Valmorri, A. Riccobon, R. Ridolfi; Istituto Scientifico Romagnolo per
lo Studio e la Cura dei Tumori, Meldola-Forlì, Italy
 
Abstract:
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.