Search

Purpose: The NIPU-trial investigates the effect of adding the telomerase vaccine UV1 to treatment with ipilimumab and nivolumab for patients with pleural mesothelioma (PM)., Methods: In this phase 2 open-label trial, patients with PM progressing after first-line chemotherapy were randomised to receive ipilimumab and nivolumab alone (arm B) or combined with UV1 (arm A). The primary endpoint was progression-free survival (PFS) as determined by BICR. It was estimated that 69 PFS events were needed to detect a hazard ratio (HR) of 0.60 with 80% power and a one-sided alpha level of 0.10., Results: 118 patients were randomised. The median PFS determined by blinded independent central review (BICR) was 4.2 months (95%CI 2.9-9.8) in arm A and 4.7 months (95%CI 3.9-7.0) in arm B (HR 1.01, 80%CI 0.75-1.36 P = 0.979), after a median follow-up of 12.5 months (95%CI 9.7-15.6). The investigator-determined median PFS was 4.3 months (95%CI 3.0-6.8) in arm A and 2.9 months (95%CI 2.4-5.5) in arm B (HR 0.60, 80%CI 0.45-0.81 P = 0.025). Confirmed objective response rate (ORR) by BICR was 31% in arm A and 16% in arm B (odds ratio 2.44 80%CI 1.35-4.49 P = 0.056). After a median follow-up time of 17.3 months (95%CI 15.8-22.9), the OS was 15.4 months (95%CI 11.1-22.6) in arm A and 11.1 months (95%CI 8.8-18.1) in arm B, (HR 0.73, 80%CI 0.53-1.0, P = 0.197)., Conclusion: The primary endpoint was not met. Predefined analyses of response rates are in favour of adding the vaccine., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Vilde Drageset Haakensen - Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: AstraZeneca, Roche, Takeda, Pfizer, BMS, MSD, Janssen. Participation on a Data Safety Monitoring Board or Advisory Board: Novartis, Astra Zeneca, BMS. Leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid: Board member of lung cancer patient organization from 2022. Support from the South-Eastern Norway Regional Health Authorities, grant number 2021083. Maria Bjaanæs - Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: AstraZeneca, Pfizer, BMS. Weronika Maria Szejniuk – none declared. Solfrid Thunold - Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: BMS. Susana Cedres - Participation on a Data Safety Monitoring Board or Advisory Board: F. Hoffmann La Roche AG, MSD Oncology, Pfizer, Amphera, Boehringer Ingelheim, BMS Wee L Chin – none declared. Tonje Sofie Dalen – none declared. Saima Farooqi - Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Merck. Oscar Grundberg – none declared. Åslaug Helland - All support for the present manuscript (e.g., funding, provision of study materials, medical writing, article processing charges, etc.): South-Eastern Norway Regional Health Authorities, grant number 202007 and 2016056, Ultimovacs, BMS. Grants or contracts from any entity: Roche, InCyte, Astra Zeneca, Merck, Novartis, Eli Lilly, GSK, Illumina, Nanopore. Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: AstraZeneca, Janssen, Medicovver, Bayer, Eli Lilly, MSD, BMS, Merck, Sanofi, Abbvie, Pfizer, Takeda, Novartis, Roche. Participation on a Data Safety Monitoring Board or Advisory Board: AMGEN (DSMC), AdBoard: Roche, AstraZeneca, Pfizer, Janssen, BMS, EliLilly, Abbvie, Bayer, Sanofi, Merck, Takeda. Leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid: Board member of lung cancer patient organization until 2022 Marius Lund Iversen – none declared. Anna K Nowak - Grants or contracts from any entity: Astra Zeneca. Participation on a Data Safety Monitoring Board or Advisory Board: AstraZeneca, BMS, Douglas Pharmaceuticals Åsa Kristina Öjlert – none declared. Jens Benn Sørensen - Participation on a Data Safety Monitoring Board or Advisory Board: BMS, Merck, Astra Zeneca., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Recent clinical trials with immune checkpoint inhibitors (ICIs) have shown that a subgroup of patients with malignant pleural mesothelioma (MPM) could benefit from these agents. However, there are no accurate biomarkers to predict who will respond. The aim of this study was to assess the accuracy of exhaled breath analysis using electronic technology (eNose) for discriminating between responders to ICI and non-responders., Methods: This proof-of-concept prospective observational study was part of an intervention study (INITIATE) in patients with recurrent MPM who were treated with nivolumab (anti-PD-1) plus ipilimumab (anti-CTLA-4). At baseline and after six weeks of treatment, breath profiles were collected by an eNose. Modified Response Evaluation Criteria in Solid Tumors were used to assess efficacy at 6-month follow-up. For data processing and statistics, we used independent t-test analyses followed by linear discriminant and receiver-operating characteristic (ROC) analysis., Results: Exhaled breath data of 31 MPM patients who received nivolumab plus ipilimumab were available at baseline. There were 16 with and 15 without a response after 6 months of treatment. At baseline, breath profiles significantly differed between responders and non-responders, with a cross validation value of 71%. The ROC-AUC after internal cross-validation was 0.90 (confidence interval: 0.80-1.00)., Conclusion: An eNose is able to discriminate at baseline between responders and non-responders to nivolumab plus ipilimumab in MPM, thereby potentially identifying a subgroup of patients that will benefit from ICI treatment., Competing Interests: Conflict of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: R.d.V. receives personal fees and has a substantial interest in the start-up company Breathomix BV, which produces eNoses linked to an online cloud solution. P.J.S. is a scientific adviser and has an officially non-substantial interest in the start-up company Breathomix BV that produces eNoses and accompanying cloud algorithms. P.B. reports grants from BMS, grants from MSD, outside the submitted work. All remaining authors declared no conflicts of interest., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: In preclinical models, statins showed vaccine adjuvant activities and synergized with PD-1 inhibitors. We analyzed the impact of statin treatment on clinical outcome in thoracic cancer patients treated with PD-1 inhibitors., Methods: A total of 82 malignant pleural mesothelioma (MPM) and 179 advanced non-small cell lung cancer (aNSCLC) patients treated with PD-1 inhibitors as second or further line treatment were examined. Seventy-seven MPM patients treated with standard chemotherapy were analyzed as control cohort. Objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were calculated., Results: Among 253 patients with available data, statin use was associated with increased ORR (32% versus 18%, P = .02), PFS (median 6.7 versus 2.9 months, hazard ratio [HR] 0.57, 95% CI 0.39-0.83, P < .01), and OS (median 13.1 versus 8.7 months, HR 0.67, 95% CI 0.45-1.00, P = .05). In the control MPM cohort treated with chemotherapy (n = 77), no association was found. MPM patients who used statins showed improved ORR (22% versus 6%, P = .05), PFS (median 6.7 versus 2.4 months, P < .01), and OS (median not reached versus 6.0 months, P = .01). In aNSCLC patients, statin use was associated with improved ORR (40% versus 22%, P = .04) and PFS (median 7.8 versus 3.6 months, P = .03), but no significant difference in OS was found (median 13.1 versus 10.1 months, P = .30). Multivariable analysis confirmed the correlation between statin use and better PFS and OS in MPM and better PFS in aNSCLC. In the whole cohort, high but not low/moderate-intensity statins were associated with better OS compared to no user (P = .02 and P = .59, respectively)., Conclusions: Our study showed that statins are associated with better clinical outcome in MPM and aNSCLC patients treated with PD-1 inhibitors in an intensity-dependent manner., Competing Interests: Conflict of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: 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. Relevant financial activities outside the submitted work: DD reports receiving speakers fee from BMS, Roche, Pfizer, and Novartis. RC reports consulting for Roche, MSD, Boehringer Ingelheim and receiving speakers fee from BMS, Roche, Pfizer, Boehringer Ingelheim, Novartis. JA 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, Astra Zeneca and Roche. RB is a consultant/advisory board member for Astra Zeneca, Boehringer Ingelheim, Novartis, MSD, Otsuka, Eli-Lilly, Roche. The other authors have no conflicts of interest to declare., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Aim: Severe neurological and endocrine toxicities are well recognised adverse events of immune checkpoint inhibitors. However, the underlying pathophysiology is poorly understood, and classical circulating markers are often non-informative, making it difficult to obtain a precise diagnosis and to initiate timely and effective treatment. Here we investigated immune-modulating activity in the plasma of a mesothelioma patient who developed fatal neuroendocrine toxicity characterised by insulin-dependent diabetes, hypophisitis and a myasthenia-like syndrome while on treatment with the dual PD1 and TIM3 blockade., Methods: We used an in vitro functional assay for unbiased detection of plasma dendritic cell-modulating activity, followed by cytokine quantification by the Cytokine Bead Array., Results: Immunosuppressive treatment as per established guidelines could not prevent the fatal outcome. Patient's plasma contained a dendritic cell-stimulating activity that induced specific markers (CD25+) compatible with T-helper 17 stimulation. Consistently, elevated levels of interleukin 17 (IL17A), but no other cytokines, were identified in the patient's plasma but not in controls (healthy volunteers and patients treated with immunotherapy without neuroendocrine toxicities)., Conclusion: If confirmed in larger series, these data suggest IL17 as a candidate diagnostic and therapeutic target in the management of high-grade neuroendocrine immune-related adverse events., Competing Interests: Conflict of interest statement GC reports expert roles in advisory boards of Pfizer, Seattle Genetics, Roche, Ellipsis, and Daiichi Sankyo e Novartis. All other authors declare that they have no competing interests., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Introduction: Very little is known about the characteristics of mesothelial tumours in the paediatric population. In adults with malignant mesothelioma, the pemetrexed-based regimen with cytoreductive surgery (CRS) is a standard of care in limited tumours, but long-term survival is uncommon., Material and Methods: The European Cooperative Study Group on Pediatric Rare Tumors (EXPeRT) retrospectively reviewed children, adolescents and young adults (≤21 year) diagnosed with mesothelial tumours treated between 1987 and 2018., Results: Thirty-three patients were identified, 15 male and 18 female patients. One patient's exposure to asbestos was documented. Primary tumour was mainly in the peritoneum (23 patients). Histology was multicystic mesothelioma of the peritoneum (MCM) (six patients) or malignant mesothelioma (MM) (27 patients). Among MM, the first-line treatment comprised preoperative chemotherapy (14 cases), surgery only (three cases), chemotherapy only (five cases), adjuvant chemotherapy (three cases) or palliative treatment (two cases). The response rate to cisplatin-pemetrexed was 50% (6/12 cases). CRS with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) was performed in 19 patients (upfront in three, after neoadjuvant therapy in 12, or after tumour progression in six patients, including three twice). After a median follow-up of 6.7 years (range, 0-20), five-year overall and event-free survivals were 82.3% (95% CI, confidential interval ((CI), 67.8-99.9) and 45.1% (95% CI, 28.4-71.7), respectively. All patients with MCM are alive after surgery (five patients) and CRS-HIPEC (one patient)., Conclusions: Paediatric mesothelioma is exceptional and seems to be different from its adult counterpart with few asbestos exposures, more peritoneal primary, and a better outcome. The cisplatin-pemetrexed regimen showed promising efficacy. Relapses could be salvaged with active therapy including CRS-HIPEC., (Copyright © 2020 Elsevier Ltd. All rights reserved.)