159P - Unveiling the impact of DC vaccination on systemic immunity in advanced malignant melanoma: Preliminary results from the ABSIDE study

Background

Malignant melanoma (MM) accounts for 80% of skin cancer-related deaths despite representing only 4% of cases. Immunotherapy has achieved promising results regarding recurrence-free survival (RFS) and overall survival (OS) in patients with MM. Thus, dendritic cell vaccination (DCvax) represents an anti-tumor autologous cell therapy with an excellent toxicity profile.

Methods

We designed a phase II trial to provide an autologous tumor lysate-loaded DCvax combined with immunomodulating radiotherapy (RT) and/or pre-leukapheresis IFN-α in patients (pts) with unresectable stage III or stage IV MM. Pts were randomised in 4 ARMS (Arm A: DCvax +RT; Arm B: DCvax + IFN-α; Arm C: DCvax +RT +IFN-α; Arm D: DCvax) to: a) determine the safety of the DCvax in combination with IFN-α and/or RT; b) select the regimen with the highest immune-related Disease Control Rate (irDCR) used in combination with DCvax; c) compare immunologic efficacy between the different treatment arms, defined as the proportion of subjects developing positive DTH to the Autologus Tumor Lysate (ATL) and/or KLH, along with tumour antigen-specific circulating immune effectors quantification at the baseline and after at least 4 DCvax doses. Furthermore, an in-depth study of DC recovery, functionality, and a full characterization of pt’s circulating immune profile was conducted. The findings were correlated with pt’s clinical outcome.

Results

Overall, 34 pts were enrolled from 2013 to the end of 2022, of whom only 29 were evaluable and fairly balanced for sex. Arm A pts (n=7): median age 65.8 years (yrs), OS 5.3 months (mos) (95% CI: 2.5-NR); arm B (n=8): age 54.8 yrs, OS 11.2 mos (1.2-NR); arm C (n=7): age 69.6 yrs, OS 8 mos (2-NR); arm D (n=7): age 66.9 yrs, OS 20.7 mos (11.7-NR). Notably, pts treated with the vaccine alone or with IFN-α pre-leukapheresis exhibited a positive DTH test in 83% and 71% of cases, respectively. Furthermore, the immune-related response to therapy observed in our cohort showed a higher irDCR in arm D (DCvax only) at 57% (p = 0.099).

Conclusions

We demonstrate the safety profile of DCvax in advanced MM pts and highlight unique immunomodulatory traits, paving the way for new therapeutic approaches combining immunotherapy and autologous cell therapies.

Clinical trial identification

EudraCT 2012-001410-41.

Legal entity responsible for the study

IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Meldola, Italy.

Funding

This work was partly supported thanks to the contribution of 5x1000 by the Italian Ministry of Health.

Disclosure

All authors have declared no conflicts of interest.