Response and survival of metastatic melanoma patients treated with immune checkpoint inhibition for recurrent disease on adjuvant dendritic cell vaccination

Abstract

Response and survival of metastatic melanoma patients treated with immune checkpoint inhibition for recurrent disease on adjuvant dendritic cell vaccination, ABSTRACTVaccination with autologous dendritic cells (DC) loaded ex vivo with melanoma-associated antigens is currently being tested as an adjuvant treatment modality for resected locoregional metastatic (stage III) melanoma. Based on its mechanism of action, DC vaccination might potentiate the clinical efficacy of concurrent or sequential immune checkpoint inhibition (ICI). The purpose of this study was to determine the efficacy of ICI administered following recurrent disease during, or after, adjuvant DC vaccination. To this end, we retrospectively analyzed clinical responses of 51 melanoma patients with either irresectable stage III or stage IV disease treated with first-or second-line ICI following recurrence on adjuvant DC vaccination. Patients were analyzed according to the form of ICI administered: PD-1 inhibition monotherapy (nivolumab or pembrolizumab), ipilimumab monotherapy or combined treatment with ipilimumab and nivolumab. Treatment with first-or second-line PD-1 inhibition monotherapy after recurrence on adjuvant DC vaccination resulted in a response rate of 52%. In patients treated with ipilimumab monotherapy and ipilimumab-nivolumab response rates were 35% and 75%, respectively. In conclusion, ICI is effective in melanoma patients with recurrent disease on adjuvant DC vaccination. ARTICLE HISTORY

Discontinuation of BRAF/MEK-Directed Targeted Therapy after Complete Remission of Metastatic Melanoma—A Retrospective Multicenter ADOReg Study

“…Response to ICI in the second-line setting varies from 15.4% in case of pembrolizumab to 12% for combined IPI + Nivo treatment [ 38 ]. After DC-vaccination [ 39 ] or first-line ICI [ 6 ] response rates have been reported to be much higher (35–72%). By contrast, median PFS after progression upon combined TT has been reported to be 2.6 months for anti-PD-1 monotherapy vs. 2.0 months for a combination of anti-PD-1 and anti-CTLA-4 therapy.…”

Research progress on dendritic cell vaccines in cancer immunotherapy

“…The combination of a DC vaccine with immune checkpoint inhibitors (ICIs) has been shown to be effective in treatment of melanoma patients. Even after recurrence in patients who received adjuvant DC vaccination, treatment with first- or second-line PD-1 inhibitor monotherapy resulted in a response rate of 52% [ 97 ]. A clinical study demonstrated complete and long-lasting clinical responses in patients with immune checkpoint inhibitor-resistant, metastatic melanoma treated with adoptive T cell transfer combined with DC vaccination, with clinical responses induced by tumor-infiltrating lymphocyte (TIL) therapy combined with DC vaccination seen in 4 out of 4 treated metastatic melanoma patients who previously failed ICI therapy [ 98 ].…”

Recent Advances in Experimental Dendritic Cell Vaccines for Cancer

“…The response rate with pembrolizumab or nivolumab alone was 52%, and 35% responded to ipilimumab monotherapy. The effectiveness of ipilimumab in combination with nivolumab was 75% ( 5 ).…”

“…Once in the lymph nodes, DCs carry out antigen presentation for CD4 + and CD8 + T-cells, activating the cell-mediated and humoral adaptive immune system. Moreover, these vaccines can act as a safe adjunct to complex anticancer therapy, thus enhancing the therapeutic effects of chemotherapy (4) or other immunotherapeutic methods such as immune checkpoint inhibitors (ICIs) (5). Sipuleucel-Tthe first FDA-approved immunotherapeutic drug based on autologous DCs treated with the recombinant prostatic acid phosphatase (PAP) and granulocyte-macrophage colonystimulating factor (GM-CSF) fusion, has shown not only no toxic effects, but also positive prospects in therapeutic approaches for the treatment of prostate cancer (6).…”