Joachim G. J. V. Aerts, MD, PhD, professor, pulmonary oncology, head, Department of Pulmonary Medicine, Erasmus MC Cancer Institute, discusses the rationale for conducting the phase 3 DENIM trial (NCT03610360) in patients with mesothelioma, highlighting the importance of focusing investigational efforts onto the dendritic cells.

Data from the study were presented at the International Association for the Study of Lung Cancer (IASLC) 2023 World Conference on Lung Cancer. In the DENIM trial, investigators assessed the potential of an allogeneic dendritic cell vaccine maintenance therapy to stimulate immune responses in patients with mesothelioma.

Mesothelioma is a disease characterized by an overwhelmingly poor prognosis, Aerts begins. Despite the occasional positive responses seen in patients treated with PD-1 inhibitors, the majority of patients either do not respond to immunotherapy at all or experience only temporary benefits, Aerts explains. This limited success can be attributed to the apparent absence of robust immune activation within the tumor microenvironment, he notes. To address this unmet need, investigators embarked on a novel treatment approach aimed at stimulating immune activation by administering dendritic cells to patients, Aerts adds.

Dendritic cells represent the most potent antigen-presenting cells in the human body, he expands. Therefore, the investigators’ strategy involved loading dendritic cells with an antigen lysate containing specific mesothelioma antigens, he explains. The primary objective of the investigation was to trigger a robust immune response, with the hope of eliciting the activation of CD8-positive T cells, which are known for their antitumor capabilities, Aerts says. 

Overall, this treatment approach was driven by the recognition that conventional treatments have fallen short in harnessing the immune system's full potential against mesothelioma, Aerts continues. By leveraging dendritic cells and their remarkable antigen presentation abilities, investigators aimed to initiate a more effective and sustained immune response within patients, ultimately improving their prospects, Aerts concludes.

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Joachim G. J. V. Aerts, MD, PhD, discusses the rationale for conducting the phase 3 DENIM trial in patients with mesothelioma, highlighting the importance of focusing investigational efforts onto the dendritic cells.


Dr Aerts on the Rationale for the DENIM Trial in Mesothelioma

Joachim G. J. V. Aerts, MD, PhD, professor, pulmonary oncology, head, Department of Pulmonary Medicine, Erasmus MC Cancer Institute, Rotterdam, Netherlands, discusses findings from the phase 3 DENIM trial (NCT03610360) in patients with mesothelioma, which was presented at the 

International Association for the Study of Lung Cancer (IASLC) 2023 World Conference on Lung Cancer

The phase 3 DENIM trial evaluated the ability of an allogenic dendritic cell vaccine to induce immune responses in patients with mesothelioma when used as maintenance therapy. Patients who had achieved stable disease or a response to their last chemotherapy were randomly assigned 1:1 to the dendritic cell vaccine plus best supportive care (BSC) or BSC alone.

Results showed that the trial did not meet its primary end point of improved overall survival (OS), Aerts reports, as there was no significant increase in OS with dendritic cell therapy vs BSC alone. The median OS in the dendritic cell arm was 16.9 months (95% CI, 12.4-20.4) compared with vs 18.3 months with BSC alone (HR, 1.10 [0.765-1.572]; 95% CI, 14.3-21.9). Likewise, the median progression-free survival was 166 days (95% CI, 99-178) for the vaccine group and 99 days (95% CI, 93-136) for the BSC group.

Additionally, flow cytometric analyses demonstrated an increase in the activation and proliferation of CD4-positive T-cells in peripheral blood with dendritic cell therapy, Aerts states. This was shown to correlate with PFS (

 = 0.0007), he adds. It is hypothesized that the prolonged interval between the start of dendritic cell vaccination and cessation of chemotherapy may have contributed to unfavorable responses, Aerts explains, as patients had already begun to experience progression. Consequently, the vaccine might find a more suitable role as a second-line treatment, he concludes.

In terms of safety, the dendritic cell vaccine displayed a favorable toxicity profile. Of the 10% of serious adverse effects (AEs) observed, none were attributed to the vaccine. Injection site or infusion reactions, which included skin induration, itching, and occasional fever on the day of injection, were observed. These AEs were primarily associated with the intradermal administration of the vaccine.

Joachim G. J. V. Aerts, MD, PhD, discusses findings from the phase 3 DENIM trial in patients with mesothelioma, which was presented at the International Association for the Study of Lung Cancer 2023 World Conference on Lung Cancer.

Joachim G. J. V. Aerts, MD, PhD

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