As reported in The Lancet Oncology by Aerts et al, the phase II/III DENIM trial showed no overall survival benefit with a treatment comprising dendritic cells loaded with allogeneic tumor cell lysate (called MesoPher) plus best supportive care vs best supportive care alone as maintenance therapy in patients with unresectable pleural mesothelioma after chemotherapy.
Study Details
In the open-label trial, 176 patients from four sites in Belgium, France, and the Netherlands were randomly assigned between June 2018 and June 2021 to receive MesoPher plus best supportive care (n = 88) or best supportive care alone (n = 88). MesoPher treatment consisted of a maximum of five infusions with 25 × 106 dendritic cells given on days 1, 15, and 29, and weeks 18 and 30. Patients had nonprogressing disease after four to six cycles of standard chemotherapy with pemetrexed at 500 mg/m2 plus cisplatin at 75 mg/m2 or carboplatin at area under the curve = 5.
The primary outcome measure of the trial was overall survival.
Overall Survival
As of data cutoff in June 2023, after a median follow-up of 15.1 months (interquartile range = 9.5–22.4 months), median overall survival was 16.8 months (95% confidence interval [CI] = 12.4–20.3 months) in the MesoPher/best supportive care group vs 18.3 months (95% CI = 14.3–21.9 months) in the best supportive care alone group (hazard ratio [HR] = 1.10, 95% CI = 0.77–1.57, P = .62). Rates at 12 and 24 months were 62% vs 67% and 43% vs 51%, respectively.
Median progression-free survival was 5.4 months (95% CI = 3.2–5.8 months) in the MesoPher/ best supportive care group vs 3.2 months (95% CI = 3.0 months–4.5 months) in the best supportive care alone group (HR = 0.90, 95% CI = 0.66–1.23). Immune checkpoint inhibitor therapy—primarily anti–PD-1 antibodies—was subsequently received by 60% of patients in the MesoPher/best supportive care group and 58% of those in the best supportive care alone group.
Adverse Events
The most commonly reported grade 3 or 4 adverse events were chest pain (3%) and anemia (2%) in the MesoPher/best supportive care group, and dyspnea, chest pain, nausea, decreased appetite, and pneumonia (2% each) in the best supportive care alone group. Treatment-related infusion reactions and injection site reactions occurred in 74% and 84% of patients in the MesoPher/best supportive care group, respectively, with all being grade 1 or 2. Serious adverse events occurred in 8% vs 9% of patients. No patients discontinued treatment due to adverse events. No treatment-related deaths were reported.
The investigators concluded, “MesoPher did not show improvement in overall survival in patients with pleural mesothelioma. Immune checkpoint therapy is now standard of care in pleural mesothelioma. Further randomized studies are needed of combinations of MesoPher and immune checkpoint therapy, which might increase efficacy without adding major toxicities.”
Joachim G. Aerts, MD, PhD, of the Erasmus Cancer Institute, Erasmus University Medical Centre, Rotterdam, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by Amphera BV and EU HORIZON. For full disclosures of the study authors, visit thelancet.com.
