Tebentafusp 100micrograms/0.5ml solution for infusion vials

Dear editorWe have reviewed the systematic review and meta-analysis conducted by Dian et al.1 which assessed the efficacy and safety of tebentafusp in patients with metastatic uveal melanoma. The r...

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BackgroundMetastatic uveal melanoma (mUM) is an aggressive malignancy with a dismal prognosis, posing a severe threat to patients’ survival and quality of life. In recent years, tebentafusp, a novel immunotherapeutic agent, has demonstrated promising potential in the management of mUM. However, inconsistencies and controversies persist in the findings of related research. This meta-analysis seeks to synthesize existing studies to more comprehensively and accurately assess the efficacy (with a primary focus on overall survival [OS]) and safety of tebentafusp in treating this disease.MethodsSystematic searches were conducted across databases including PubMed, Embase, and the Cochrane Library. Literature screening was performed rigorously in line with predefined inclusion and exclusion criteria, while the quality of included studies was assessed using the Minors scale. To ensure accuracy, data extraction was carried out independently by two researchers.ResultsThis meta-analysis included 18 studies meeting predefined criteria, encompassing patients with mUM treated with tebentafusp. These comprised 3 randomized controlled trials (RCTs) and 15 single-arm studies, with sample sizes ranging from 10 to 252 participants, and most patients being HLA-A*02:01 positive. The pooled complete response (CR) rate across 3 studies was 0.01 (1%, 95%CI: -0.01 to 0.01, p=0.18). For 15 studies, the pooled partial response (PR) rate was 0.07 (7%, 95%CI: 0.06 to 0.09, p<0.00001), and the pooled stable disease (SD) rate was 0.34 (34%, 95%CI: 0.26 to 0.41, p<0.00001), though significant heterogeneity was observed for SD (I²=84%).Across 15 studies, ORR ranged from 4.7% to 21.7%, with a pooled rate of 0.07 (7%, 95%CI: 0.06 to 0.09, p<0.0001) and low heterogeneity (I²=34%).For 16 studies, the pooled DCR was 0.46 (46%, 95%CI: 0.40 to 0.53, p<0.0001) with significant heterogeneity (I²=77%).The pooled 1-year overall survival (OS) rate across 9 studies was 0.69 (69%, 95%CI: 0.66–0.72, p<0.0001); the 2-year OS across 3 studies was 0.42 (42%, 95%CI: 0.38–0.46, p<0.0001); and the 3-year OS across 2 studies was 0.26 (26%, 95%CI:0.21–0.30, p<0.0001). Pooled median progression-free survival (PFS) across 10 studies was 2.74 months(95%CI: 2.58–2.90), and median OS across 4 studies was 19.78 months(95% CI:17.79–21.77). The pooled incidence of grade ≥3 treatment-related adverse events (TRAE) across 7 studies was 0.40 (40%, 95%CI:0.16–0.63, p=0.001) with high heterogeneity (I²=98%).The pooled incidence of cytokine release syndrome (CRS) across 8 studies was 0.86 (86%, 95%CI: 0.83–0.89, p<0.0001) with moderate heterogeneity (I²=54%). Subgroup analysis showed patients with no previous treatment received had higher PR (0.11 vs. 0.06 in previously treated patients), ORR (0.11 vs. 0.07 in previously treated patients), 1-year OS (0.72 vs. 0.63 in previously treated patients), and 2-year OS (0.45 vs. 0.39 in previously treated patients).ConclusionsTebentafusp exhibits significant clinical efficacy in mUM, with its greatest value reflected in improving long-term survival (1-year, 2-year, and 3-year OS) — a finding consistent with its FDA approval basis. While ORR and DCR provide supplementary evidence of therapeutic benefit, radiological response rates (e.g., CR, PR) are limited in fully capturing its clinical value. Safety concerns include high CRS incidence (mostly low-grade and manageable) and variable grade ≥3 TRAE rates. No previous treatment received patients may derive greater benefits. Limitations (heterogeneity, HLA-A*02:01 restriction, limited long-term data) highlight the need for more high-quality studies to validate long-term efficacy/safety, expand applicability to broader populations, and explore combination therapies. Additionally, circulating tumor DNA (ctDNA) may serve as a more sensitive efficacy biomarker than radiological responses, warranting further investigation.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD420251084090.

Abstract licence: CC BY 4.0

Metastatic uveal melanoma (mUM) is a rare disease associated with poor prognosis and limited therapeutic options. Recent studies showed that detecting ctDNA is feasible and can aid treatment decisions for patients with mUM. We systematically searched PubMed, EMBASE, and Cochrane databases for eligible studies published up to May 2025 that included patients with mUM and reported data on the association between ctDNA and survival outcomes (OS and PFS). Statistical analyses were performed using Review Manager 5.4 software. Of the initial 450 records, seven studies met eligibility, including 518 patients with mUM. At baseline, ctDNA positivity was associated with significantly worse PFS (HR 2.34; 95% CI 1.56-3.51; p 2 = 0%) and OS (HR 3.32; 95% CI 2.09-5.29; p 2 = 48%). In patients treated with tebentafusp, ctDNA clearance was associated with superior OS (HR 0.19; 95% CI 0.07-0.49; p 2 = 46%) and any decrease in ctDNA was associated with better OS (HR 0.42; 95% CI 0.22-0.80; p 2 = 0%). This meta-analysis underscores ctDNA as a potential predictor of worse survival in patients with mUM, highlighting its potential to refine risk stratification and guide treatment strategies. Trial Registration: International Prospective Register of Systematic Reviews (PROSPERO): CRD42025638076.

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ObjectiveTo evaluate efficacy and safety of tebentafusp in patients with metastatic uveal melanoma.MethodA systematic search was conducted in five databases (Pubmed, Embase, Web of Science, Scopus, and the Cochrane Library) to find articles that evaluate the effectiveness of tebentafusp in patients with metastatic uveal melanoma, from the establishment of the databases to October 13, 2025. Additionally, clinical trials were searched on clinicaltrials.gov. Meta-analyses were performed to evaluate the frequencies of progression-free survival (PFS), overall survival (OS), partial response (PR), stable disease (SD), progressive disease (PD), objective response rate (ORR), disease control rate (DCR), Cytokine release syndrome (CRS) and treatment-related adverse events (trAEs).ResultsA total of six studies were initially enrolled, involving 850 participants. Among them, 631 patients with evaluable uveal melanoma who received tebentafusp treatment were ultimately included in this meta-analysis (mean age, 60.56 years; 425 [50%] men). The median OS and PFS were 21.3 months and 3.6 months, respectively. The PR, SD, PD,ORR and DCR were 0.09 [95% confidence interval (CI), 0.05 to 0.14], 0.39 (95% CI, 0.35 to 0.43), 0.79 (95% CI, 0.32 to 0.97), 0.09 (95% CI, 0.06 to 0.13) and 0.27 (95% CI, 0.20 to 0.36), respectively. The any grade cytokine release syndrome rate, grade ≥ 3 cytokine release syndrome rate, any grade trAEs rate and grade ≥ 3 trAEs rate were 0.88 (95% CI, 0.84 to 0.91), 0.02 (95% CI, 0.01 to 0.06), 0.98 (95% CI, 0.75 to 1.00) and 0.41 (95% CI, 0.17 to 0.71), respectively. The most common adverse reactions include pyrexia 0.83 (95% CI, 0.79 to 0.86), nausea 0.58 (95% CI, 0.42 to 0.73), fatigue 0.54 (95% CI, 0.38 to 0.70), pruritus 0.72 (95% CI, 0.65 to 0.78), chills 0.60 (95% CI, 0.47 to 0.71), dry skin 0.43 (95% CI, 0.25 to 0.63), hypotension 0.41 (95% CI, 0.36 to 0.45).ConclusionThe research results show that tebentafusp exhibits modest but potentially meaningful survival benefit despite low response rates for metastatic uveal melanoma patients. Although adverse events often occur, such as cytokine release syndrome of grade three or above, they are usually manageable and controllable. Given the limitations of this study, it is crucial to conduct further multi-center randomized controlled trials and increase the sample size to further verify our results.Systematic review registrationPROSPERO: CRD420251234508. Available from https://www.crd.york.ac.uk/PROSPERO/view/CRD420251234508.

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