Unexpected High Response Rate to Traditional Therapy after Dendritic Cell‐Based Vaccine in Advanced Melanoma: Update of Clinical Outcome and Subgroup Analysis

Abstract

We reviewed the clinical results of a dendritic cell-based phase II clinical vaccine trial in stage IV melanoma and analyzed a patient subgroup treated with standard therapies after stopping vaccination. From 2003 to 2009, 24 metastatic melanoma patients were treated with mature dendritic cells pulsed with autologous tumor lysate and keyhole limpet hemocyanin and low-dose interleukin-2. Overall response (OR) to vaccination was 37.5% with a clinical benefit of 54.1%. All 14 responders showed delayed type hypersensitivity positivity. Median overall survival (OS) was 15 months (95% CI, 8–33). Eleven patients underwent other treatments (3 surgery, 2 biotherapy, 2 radiotherapy, 2 chemotherapy, and 4 biochemotherapy) after stopping vaccination. Of these, 2 patients had a complete response and 5 a partial response, with an OR of 63.6%. Median OS was 34 months (range 16–61). Our results suggest that therapeutic DC vaccination could favor clinical response in patients after more than one line of therapy.

Immune response and long-term clinical outcome in advanced melanoma patients vaccinated with tumor-mRNA-transfected dendritic cells

“…Other groups have also reported favorable responses in patients receiving other therapies after vaccination. 72 These observations strengthen the hypothesis that these therapies may synergize. The checkpoint inhibitor therapy was started 3 and 5 y after vaccination, respectively, in patient M22 and M109.…”

Vaccination with autologous dendritic cells loaded with autologous tumor lysate or homogenate combined with immunomodulating radiotherapy and/or preleukapheresis IFN-α in patients with metastatic melanoma: a randomised “proof-of-principle” phase II study

“…Like de Vries et al [17], we saw that patients who developed anti-tumor immunity after vaccination experienced a better clinical outcome [16,18]. In particular, we observed that patients developing delayed type hypersensitivity (DTH) against autologous tumor lysate or keyhole lympet hemocyanin (KLH) after at least four courses of the vaccine showed a median overall survival (OS) of 22.9 months compared to the 4.8 months of DTH-negative cases (Log-rank test, p = 0.007) [16].…”

Repositioning therapeutic cancer vaccines in the dawning era of potent immune interventions

“…Higher rates of objective response were seen in vaccinated patients with melanoma or RCC who received concurrent cytokine treatment, compared to patients who were being treated with cytokines alone [95,96]. While such studies are exciting, the results need to be confirmed in larger and adequately controlled trials that are quite difficult to conduct, due to the niche nature of the clinical indications and the toxicities associated with cytokine therapy.…”