Outcome prediction based on \[18F\]FDG PET/CT in patients with pleural mesothelioma treated with ipilimumab and nivolumab +/- UV1 telomerase vaccine

Our plain-English summary of Outcome prediction based on [18F]FDG PET/CT in patients with pleural mesothelioma treated with ipilimumab and nivolumab +/- UV1 telomerase vaccine, by S. Thunold, E. Hernes, S. Farooqi, et al (European Journal of Nuclear Medicine and Molecular Imaging, 2025).

The study

• Authors: S. Thunold, E. Hernes, S. Farooqi, Å.K. Öjlert, R.J. Francis, A.K. Nowak, W.M. Szejniuk, S.S. Nielsen, S. Cedres, M.S. Perdigo, J.B. Sørensen, C. Meltzer, L.T.G. Mikalsen, Å. Helland, E. Malinen, V.D. Haakensen
• Journal: European Journal of Nuclear Medicine and Molecular Imaging
• Published: 2025;52(2):693-707
• Type of article: Randomized trial
• Cited by: 4 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Purpose: The introduction of immunotherapy in pleural mesothelioma (PM) has highlighted the need for effective outcome predictors. This study explores the role of [18F]FDG PET/CT in predicting outcomes in PM treated with immunotherapy.

Methods: Patients from the NIPU trial, receiving ipilimumab and nivolumab +/- telomerase vaccine in second-line, were included. [18F]FDG PET/CT was obtained at baseline (n = 100) and at week-5 (n = 76). Metabolic tumour volume (MTV) and peak standardised uptake value (SUVpeak) were evaluated in relation to survival outcomes. Wilcoxon rank-sum test was used to assess differences in MTV, total lesion glycolysis (TLG), maximum standardised uptake value (SUVmax) and SUVpeak between patients exhibiting an objective response, defined as either partial response or complete response according to the modified Response Criteria in Solid Tumours (mRECIST) and immune RECIST (iRECIST), and non-responders, defined as either stable disease or progressive disease as their best overall response.

Results: Univariate Cox regression revealed significant associations of MTV with OS (HR 1.36, CI: 1.14, 1.62, p < 0.001) and PFS (HR 1.18, CI: 1.03, 1.34, p = 0.02), while multivariate analysis showed a significant association with OS only (HR 1.35, CI: 1.09, 1.68, p = 0.007). While SUVpeak was not significantly associated with OS or PFS in univariate analyses, it was significantly associated with OS in multivariate analysis (HR 0.43, CI: 0.23, 0.80, p = 0.008). Objective responders had significant reductions in TLG, SUVmax and SUVpeak at week-5.

Conclusion: MTV provides prognostic value in PM treated with immunotherapy. High SUVpeak was not associated with inferior outcomes, which could be attributed to the distinct mechanisms of immunotherapy. Early reductions in PET metrics correlated with treatment response.

Study Registration: The NIPU trial (NCT04300244) is registered at clinicaltrials.gov. https://classic.

Clinicaltrials: gov/ct2/show/NCT04300244?cond=Pleural+Mesothelioma&cntry=NO&draw=2&rank=4.

© 2024. The Author(s).

In plain English

This study analysed PET/CT scans from the NIPU trial, in which patients with pleural mesothelioma progressing after platinum chemotherapy received ipilimumab and nivolumab, with or without UV1 telomerase vaccine. Baseline scans from 100 patients in Norway, Denmark, Spain and Australia were compared with survival. Changes by week 5 (76 patients) were compared with CT tumour response. Patients with lower metabolic tumour volume (MTV) had significantly better overall and progression-free survival. In adjusted analysis of standard 60-minute baseline scans, higher log-scale MTV was associated with shorter overall survival (hazard ratio 1.35, 95% CI 1.09 to 1.68) but not significantly with progression-free survival. On 120-minute scans it was significant only for progression-free survival. Higher peak tracer uptake (SUVpeak) was not linked to worse outcomes. In adjusted 60-minute analysis, higher log-scale SUVpeak was associated with better overall survival (hazard ratio 0.43, CI 0.23 to 0.80). Changes in PET measures by week 5 differed significantly between responders and non-responders. Median uptake measures fell in responders and rose in non-responders, though a few responders' measures rose. The authors concluded that MTV is an outcome predictor in this setting. They noted limited sample size and visually judged tumour outlining.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Analysis of PET/CT imaging collected within a phase II, randomised, open-label, multicentre treatment trial (NIPU). Baseline PET features were compared with survival, and baseline-to-week-5 changes were compared with CT response.
• Who was studied: Patients with pleural mesothelioma with progressive disease after first-line platinum doublet chemotherapy. The trial enrolled 118. Baseline PET scans of 100 were analysed; 57 of these also had 120-minute scans, and 76 patients had a week-5 scan. Sites were Oslo (Norway), Aalborg and Copenhagen (Denmark), Barcelona (Spain) and Perth (Australia). Median age was 71, and 77 of 100 were male. Study dates are not stated in the text.
• Exposure: Not an asbestos exposure study. The treatment was nivolumab 240 mg every two weeks plus ipilimumab 1 mg/kg every six weeks, with or without the UV1 telomerase peptide vaccine. The factors studied were [18F]FDG PET measures: MTV, total lesion glycolysis (TLG), SUVmax and SUVpeak.
• Main results:
  • Among the 100 patients in the PET analysis, best overall response was partial response in 18, stable disease in 53 and progressive disease in 25. No patient had a complete response.
  • Groups with low MTV (below the median) on baseline 60-minute and 120-minute scans had significantly better overall survival and progression-free survival than groups with high MTV.
  • In univariate Cox regression, MTV was associated with overall survival (HR 1.36, CI 1.14 to 1.62, p less than 0.001) and with progression-free survival (HR 1.18, CI 1.03 to 1.34, p = 0.02). In multivariate analysis it remained significant for overall survival only (HR 1.35, CI 1.09 to 1.68, p = 0.007). These hazard ratios are for log-transformed MTV.
  • In multivariate Cox regression, MTV from the baseline 60-minute scan was significantly associated with overall survival but not with progression-free survival.
  • In multivariate Cox regression, MTV from the 120-minute baseline scan was significantly associated with progression-free survival but not with overall survival. The article's sentence is split by a page header; see text_problems.
  • SUVpeak was not significantly associated with overall or progression-free survival in univariate analyses. In multivariate analysis of the baseline 60-minute scan, it was significantly associated with overall survival, with a hazard ratio below 1 (HR 0.43, CI 0.23 to 0.80, p = 0.008, for log-transformed SUVpeak).
  • Baseline MTV, TLG, SUVmax and SUVpeak did not differ significantly between objective responders and non-responders.
  • Changes from baseline to week 5 in MTV, TLG, SUVmax and SUVpeak differed significantly between objective responders and non-responders (p = 0.01, p less than 0.001, p = 0.01 and p = 0.006, respectively).
  • From baseline to week 5, TLG fell by a median of 47% in objective responders and rose by a median of 49% in non-responders.
  • From baseline to week 5, SUVmax fell by a median of 22% in objective responders and rose by a median of 4% in non-responders.
  • From baseline to week 5, SUVpeak fell by a median of 24% in objective responders and rose by a median of 4% in non-responders.
  • The early decline was not uniform: in a few responders, volumetric PET features and FDG uptake increased at the week-5 scan.
  • In multivariate analysis, histology and ECOG performance status were significant predictors of overall survival.
  • PET features did not differ significantly between PD-L1 positive and PD-L1 negative patients in the analysis of all baseline scans.
• The authors' conclusion: The authors concluded that MTV is an outcome predictor in pleural mesothelioma treated with immunotherapy. They found that high SUVmax or SUVpeak did not suggest inferior outcomes, possibly because of the unique mechanisms of immunotherapy. An early reduction in TLG, SUVmax and SUVpeak was associated with objective response, although a minority of patients first showed an increase in PET metrics before responding.
• Limitations the authors state:
  • Limited sample size.
  • A notable proportion of scans did not meet EARL2 harmonisation specifications. A sub-analysis of compliant scans gave comparable results, except for the PD-L1 comparison and the comparison of baseline features between responders and non-responders.
  • Tumour delineation thresholds were set by investigator consensus based on visual interpretation, which may challenge the repeatability of the results.
  • Comparing MTV between baseline and week 5 is methodologically challenging, and changes in MTV should be interpreted with caution.
  • Many patients had indeterminate PD-L1 status, so the association between PET features and PD-L1 should be interpreted with caution.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Ipilimumab (Yervoy), Nivolumab (Opdivo), Immunotherapy, Multivariate Analysis, Mesothelioma.

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• Ipilimumab/Nivolumab-related Opsoclonus-Myoclonus-Ataxia Syndrome Variant in a Patient with Malignant Pleural Mesothelioma — B. Maller, E. Peguero, et al. (2018)
• NIPU: a randomised, open-label, phase II study evaluating nivolumab and ipilimumab combined with UV1 vaccination as second line treatment in patients with malignant mesothelioma — V.D. Haakensen, A.K. Nowak, et al. (2021)
• Efficacy of nivolumab and ipilimumab in patients with malignant pleural mesothelioma is related to a subtype of effector memory cytotoxic T cells: Translational evidence from two clinical trials — J.M. Mankor, M.J. Disselhorst, et al. (2020)
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