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Background: Randomized phase III trials are ongoing to investigate the efficacy of nivolumab in malignant pleural mesothelioma (MPM), but real-world data are still scarce. In this real-world study, we investigated the clinical outcomes of nivolumab treatment in pre-treated MPM patients., Methods: Data from 107 nivolumab treated MPM patients within the Dutch expanded access program were retrospectively analyzed. Treatment was independent of programmed death ligand 1 (PD-L1) expression on tumor samples. Univariable and multivariable analyses were performed to evaluate the relationship between clinically important factors, baseline peripheral blood parameters and survival. The landmark method was used to compare the outcome of patients according to their radiological response., Results: In the full cohort, the median progression-free survival (mPFS) was 2.3 months (95% CI: 1.6-2.9) and the median overall survival (mOS) was 6.7 months (95% CI: 6.2-10.0). After 12 weeks, the disease control rate (DCR) was 37% and the objective response rate (ORR) was 10%. PD-L1 status was determined in 33 patients (30%) and PD-L1 positivity (≥1%) was associated with an improved ORR (36% vs. 9%, P value 0.05), but not with PFS or OS. Low albumin was associated with worse OS (P value 0.002). Median OS was significantly longer for patients who had partial response to treatment (P value 0.0002)., Conclusions: In this real-world analysis, ORR and mOS were lower compared to those obtained in phase II trials. However, exceptional survival rates were observed in patients who had a radiological response. Although we cannot determine whether prognostic or predictive, PD-L1 expression and albumin were associated with greater response rate and may represent useful biomarkers for nivolumab treatment in MPM., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tlcr-19-686). DWD reports personal fees from Roche, BMS, MSD, Pfizer, Astra Zeneca and Novartis outside the submitted work. RC reports speakers fee from Roche, Pfizer and BMS, personal fees from Advisory Board MSD and Advisory Board Roche outside the submitted work. JAB reports other from Bristol-Meyers Squibb, MSD B.V., F. Hoffmann- La Roche Ltd. during the conduct of the study. PB reports other from Bristol-Myers Squibb, MSD B.V., AstraZeneca, Takeda outside the submitted work. JGJVA reports personal fees and non-financial support from MSD, personal fees from BMS, Boehringer Ingelheim, Amphera, Eli-Lilly, Takeda, Bayer, Roche, Astra Zeneca outside the submitted work; in addition, JGJVA has a patent allogenic tumor cell lysate licensed to Amphera, a patent combination immunotherapy in cancer pending, and a patent biomarker for immunotherapy pending; JGJVA serves as an unpaid editorial board member of Translational Lung Cancer Research from Sep 2019 to Sep 2021. The other authors have no conflicts of interest to declare. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (2020 Translational Lung Cancer Research. All rights reserved.)

Background: Malignant pleural mesothelioma (MPM) is an aggressive, treatment resistant neoplasm. The current treatment, consisting of antifolate and platinum-based chemotherapy, improves the median overall survival with only 3 months. Adjuvant bevacizumab generates an additional 2 months survival benefit. Checkpoint inhibitors (CI) have shown promising clinical effects in only a minority of patients. A possible reason is that MPM patients have low numbers of tumor-infiltrating CD8 + T-cells. Dendritic cell (DC) therapy can induce an immune response and activate tumor-specific CD8 + T-cells. Allogeneic mesothelioma tumor-lysate loaded DC therapy has proven effective in mice and safe and feasible in humans. We have designed a randomized, phase II/III, multicenter, open-label trial to examine the efficacy of DC therapy in humans with histologically proven MPM., Methods: In this open-label, multicenter, randomized phase II/III trial patients will be randomized to receive either DC therapy plus best supportive care (BSC) or BSC alone according to the discretion of the local investigator after first line chemotherapy treatment. The primary end point will be overall survival. The secondary endpoints will be safety and tolerability, progression-free survival, overall response rate and quality of life., Discussion: This phase II/III trial will determine whether DC therapy in patients with MPM is safe and effective as a maintenance treatment and subsequently might be a new treatment option for MPM., Competing Interests: Conflicts of Interest: JGJV Aerts reports receiving commercial research grants from Amphera and Roche, holds ownership interest (including patents) in Amphera BV, and is a consultant/advisory board member for Amphera, Boehringer Ingelheim, Bristol-Myers Squibb, Eli-Lilly, MSD, Takeda, Bayer en Astra-Zeneca and Roche. R. Cornelissen reports consulting for Roche, MSD, Boehringer Ingelheim and receiving speakers fee from BMS, Roche, Pfizer, Boehringer Ingelheim, Novartis. P. Baas reports receiving advisorships from Merck and BMS. The other authors have no conflicts of interest to declare.