Dendritic Cell Therapy Offers No Survival Advantage in Pleural Mesothelioma

— Immunotherapy may have been given too late, researchers suggested

A scanning electron microscope image of a dendritic cell

Maintenance treatment with a novel dendritic cell immunotherapy after chemotherapy did not improve survival outcomes for patients with pleural mesothelioma in the phase II/III DENIM study.

Over a median 15 months of follow-up, the addition of maintenance dendritic cell immunotherapy to best supportive care did not improve overall survival versus best supportive care alone (median 16.8 vs 18.2 months, respectively; HR 1.10, 95% CI 0.77-1.57, P=0.62) or progression-free survival (5.4 vs 3.2 months; HR 0.90, 95% CI 0.66-1.23, P=0.60).

In a subgroup analysis of the 176-patient trial, however, progression-free survival was significantly better with the dendritic cell therapy in patients with non-epithelioid histology (5.7 vs 2.9 months; HR 0.27, 95% CI 0.11-0.69, P=0.015), researchers led by Joachim Aerts, MD, PhD, of the Erasmus Cancer Institute in Rotterdam, the Netherlands, reported in .

"This finding should be interpreted cautiously in light of the small number of patients [n=28] in the non-epithelioid group," Aerts and colleagues wrote. "Although the study did not meet its primary outcome of improved overall survival, we found broad immune activation and a good safety profile."

In an accompanying the study, Marjorie Zauderer, MD, of Memorial Sloan Kettering Cancer Center in New York City, and Ibiayi Dagogo-Jack, MD, of Harvard ľֱ School in Boston, said one reason the study did not meet its primary endpoint may have been the long interval between the last chemotherapy session and the start of maintenance therapy.

The dendritic cell treatment, branded as by its developer, consisted of autologous monocyte-derived dendritic cells loaded with an allogeneic tumor cell lysate. Patients randomized to the treatment group underwent a leukapheresis session 5-8 weeks after the last cycle of chemotherapy. After 10 days of production and an additional 3 weeks for sterility checks and other batch release procedures, the vials were frozen and shipped to the investigational site.

Treatment with the cell immunotherapy began 9-13 weeks after the last chemotherapy cycle. Patients received up to five infusions, with treatments administered on days 1, 15, and 29, and weeks 18 and 30. At each treatment, patients received an injection of 25×10⁶ dendritic cells. Two-thirds of the cells were administered intravenously, and a third were injected intradermally.

"In DENIM, the interval between the start of the last chemotherapy and day 1 of treatment with MesoPher was nearly 3 months, due to trial logistics and quality control measures," the editorialists wrote. "During this vulnerable 3-month gap, eight (4.5%) of 176 patients developed progressive disease, including four patients assigned to receive MesoPher."

Furthermore, they noted, 38% of patients in the treatment group and 50% of patients in the best supportive care group had evidence of disease progression on their first scan after baseline. "These early progression events raise questions about the optimal timing of maintenance therapy, particularly as studies in other difficult-to-treat tumours (e.g., small-cell lung cancer) have observed improved outcomes with earlier initiation of maintenance immunotherapy," they said.

The study authors agreed with that assessment and offered evidence to suggest that the treatment might have been more effective if given earlier.

The open-label trial included adult patients with histologically confirmed unresectable pleural mesothelioma, an Eastern Cooperative Oncology Group (ECOG) performance status score of 0–1, and non-progressing disease after four to six cycles of standard chemotherapy. A post-hoc analysis by ECOG performance status score found patients in the treatment group with a baseline score of 0 had a significantly longer progression-free survival than those with a score of 1 (8.0 vs 3.2 months, P=0.0034).

This was not the case, however, for patients in the best supportive care group (4.4 vs 3.2 months, P=0.28). "Although these are only surrogate markers, this finding might suggest that MesoPher was given too late to induce an effective sustained immune activation in the majority of patients," the researchers said.

Additional study limitations included the small sample size and open-label design, the authors said. More studies are planned, they noted. "Further randomised studies are needed of combinations of MesoPher and immune checkpoint therapy, which might increase efficacy without adding major toxicities," they concluded.

Treatment-related adverse events in the immunotherapy group were limited to infusion-related adverse reactions (including fever, chills, and fatigue), and injection site-related reactions including itching, erythema, and induration. These events were all grade 1-2, and the treatment had no negative effect on quality of life measures, the researchers reported.

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    Jeff Minerd is a freelance medical and science writer based in Rochester, NY.


The study was funded by Amphera BV and EU HORIZON.

Aerts reported grants, personal fees, research support, and stock ownership from Amphera and personal fees from Bristol-Myers Squibb, Eli Lilly, MSD, CureVac, and Novocure. Aerts has licensed patents for a tumor cell lysate, a combination immunotherapy, and a biomarker for immunotherapy.

Dagogo-Jack disclosed consulting fees from AstraZeneca, Bayer, BostonGene, Bristol Myers Squibb, Catalyst, Eli Lilly, Epi-Q, Genentech, Gilead, Janssen, Merus, Novocure, Pfizer, Roche, Sanofi-Genzyme, Syros, Thermo Fisher Scientific, and Xcovery. She disclosed honoraria from Foundation Medicine, Creative Education Concepts, DAVA Oncology, Total Health, Aptitude Health, American Lung Association, PeerView, and Curio.

Zauderer disclosed consulting fees from Roche Diagnostics, Curis, and Ikena; and research funding to Memorial Sloan Kettering Cancer Center from Vivace, MedImmune, Precog, GSK, Epizyme, Polaris, Sellas Life Sciences, Bristol Myers Squibb, Millenium, Curis, and Atara. Zauderer also serves as chair of the Board of Directors of the Mesothelioma Applied Research Foundation, an uncompensated position.

Primary Source

The Lancet Oncology

Aerts JG, et al "Dendritic cells loaded with allogeneic tumour cell lysate plus best supportive care versus best supportive care alone in patients with pleural mesothelioma as maintenance therapy after chemotherapy (DENIM): a multicentre, open-label, randomised, phase 2/3 study" Lancet Oncol 2024; DOI: 10.1016/S1470-2045(24)00191-8.

Secondary Source

The Lancet Oncology

Zauderer MG, Dagogo-Jack I "Refreshing the mesothelioma catalogue: Tailoring cellular therapy in the DENIM trial" Lancet Oncol 2024; DOI: 10.1016/S1470-2045(24)00291-2.