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We evaluated the prognostic value of hypoalbuminemia in context of various biomarkers at baseline, including clinical, genomic, transcriptomic, and blood-based markers, in patients with metastatic melanoma treated with anti-PD-1 monotherapy or anti-PD-1/anti-CTLA-4 combination therapy (n = 178). An independent validation cohort (n = 79) was used to validate the performance of hypoalbuminemia compared to serum LDH (lactate dehydrogenase) levels. Pre-treatment hypoalbuminemia emerged as the strongest predictor of poor outcome for both OS (HR = 4.01, 95% CI 2.10-7.67, Cox P = 2.63e-05) and PFS (HR = 3.72, 95% CI 2.06-6.73, Cox P = 1.38e-05) in univariate analysis. In multivariate analysis, the association of hypoalbuminemia with PFS was independent of serum LDH, IFN-γ signature expression, TMB, age, ECOG PS, treatment line, treatment type (combination or monotherapy), brain and liver metastasis (HR = 2.76, 95% CI 1.24-6.13, Cox P = 0.0131). Our validation cohort confirmed the prognostic power of hypoalbuminemia for OS (HR = 1.98, 95% CI 1.16-3.38; Cox P = 0.0127) and was complementary to serum LDH in analyses for both OS (LDH-adjusted HR = 2.12, 95% CI 1.2-3.72, Cox P = 0.00925) and PFS (LDH-adjusted HR = 1.91, 95% CI 1.08-3.38, Cox P = 0.0261). In conclusion, pretreatment hypoalbuminemia was a powerful predictor of outcome in ICI in melanoma and showed remarkable complementarity to previously established biomarkers, including high LDH., (© 2024. The Author(s).)

Introduction: In a multicenter, open-label randomized phase 3 clinical trial conducted in the Netherlands and Denmark, treatment with ex vivo-expanded tumor-infiltrating lymphocytes (TIL-NKI/CCIT) from autologous melanoma tumor compared with ipilimumab improved progression-free survival in patients with unresectable stage IIIC-IV melanoma after failure of first-line or second-line treatment. Based on this trial, we conducted a cost-utility analysis., Methods: A Markov decision model was constructed to estimate expected costs (expressed in 2021€) and outcomes (quality-adjusted life years (QALYs)) of TIL-NKI/CCIT versus ipilimumab in the Netherlands. The Danish setting was assessed in a scenario analysis. A modified societal perspective was applied over a lifetime horizon. TIL-NKI/CCIT production costs were estimated via activity-based costing. Through sensitivity analyses, uncertainties and their impact on the incremental cost-effectiveness ratio (ICER) were assessed., Results: Mean total undiscounted lifetime benefits were 4.47 life years (LYs) and 3.52 QALYs for TIL-NKI/CCIT and 3.33 LYs and 2.46 QALYs for ipilimumab. Total lifetime undiscounted costs in the Netherlands were €347,168 for TIL-NKI/CCIT (including €67,547 for production costs) compared with €433,634 for ipilimumab. Undiscounted lifetime cost in the Danish scenario were €337,309 and €436,135, respectively. This resulted in a dominant situation for TIL-NKI/CCIT compared with ipilimumab in both countries, meaning incremental QALYs were gained at lower costs. Survival probabilities, and utility in progressive disease affected the ICER most., Conclusion: Based on the data of a randomized phase 3 trial, treatment with TIL-NKI/CCIT in patients with unresectable stage IIIC-IV melanoma is cost-effective and cost-saving, both in the current Dutch and Danish setting. These findings led to inclusion of TIL-NKI/CCIT as insured care and treatment guidelines. Publicly funded development of the TIL-NKI/CCIT cell therapy shows realistic promise to further explore development of effective personalized treatment while warranting economic sustainability of healthcare systems., Competing Interests: Competing interests: THB: Bristol-Myers Squibb(speaker engagement). MD: Achiles Therapeutics (consulting), Astra Zeneca (teaching), Bristol-Myers Squibb (consulting and teaching), F. Hoffman-La Roche (speaker engagement), Genentech (consulting), Merck (speaker engagement), Novartis (speaker engagement). JH: Achilles Therapeutics (Scientific Advisory Board), Amgen (funding), Asher Bio (funding), Bayer (consulting), BioNtech US (Scientific Advisory Board, funding), Bristol-Myers Squibb (consulting, funding, teaching), Eisai (consulting), ESMO IOTECH (Editor-in-chief), Gadeta (Scientific Advisory Board), Immunocore (Scientific Advisory Board), Instil Bio (consulting, teaching), Iovance Biotherapeutics (consulting, teaching), Ipsen Bioscience Inc (consulting), Merck Serono (consulting, teaching), Merck Sharp & Dohme Corporation (funding, consulting, teaching), Molecular Partners (consulting), Neogene Therapeutics (Scientific Advisory Board, shareholder), Novartis (funding, consulting, teaching), Pfizer (consulting, teaching), PokeAcel (Scientific Advisory Board), Roche/Genentech (consulting, teaching), Sanofi (consulting, teaching), Scenic (Scientific Advisory Board), Seattle Genetics (consulting), T-Knife (Scientific Advisory Board), Vaximm (Scientific Advisory Board). IMS: Adaptimmune (funding), Bristol-Myers Squibb (speaking engagement), Enara Bio (funding), Evaxion (funding), IO biotech (funding, stock, consulting), Lytix Biopharma (funding), Merck (speaking engagement and funding), Novartis (consulting), Pierre Fabre Pharmaceuticals, Inc (speaking engagement and consulting), Sanofi Pasteur Inc (speaking engagement), TILT Biotherapeutics (funding). Other authors declare to have no competing interests., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)