Document Type
Article
Publication Date
1-1-2025
Abstract
BACKGROUND: Metastatic uveal melanoma (mUM) is rare. Immune checkpoint inhibitors (ICIs) have shown modest efficacy in mUM. Tebentafusp prolonged overall survival (OS) in a phase 3 study. We aimed to investigate the efficacy and safety of the sequence of tebentafusp and ICIs.
METHODS: Patients with HLA-A * 02:01 positive mUM, or metastatic GNA11/GNAQ mutant melanocytic tumors treated with tebentafusp followed by ICIs (group 1) or the inverse sequence (group 2) at any treatment line were retrospectively identified. The primary objective was OS rate at 2 years.
RESULTS: 131 patients were included; 51 in group 1 and 80 in group 2. 30 % in group 1 % and 40 % in group 2 had normal baseline lactate dehydrogenase (LDH, p = 0.05). 94 % in group 1 % and 77 % in group 2 had multilobular liver disease (p = 0.02). Median OS was 22.4 months (95 % CI 19-24.8) in group 1 and 33.6 months (95 % CI 28.9-43) in group 2 (p = 0.004). Total median PFS was 12 months (95 % CI 10.7-18.8) in group 1 and 20.3 months (95 % CI 17.2-27.3) in group 2 (p = 0.04). The frequency of cytokine release syndrome was higher in group 2 (15 % vs 27 %). Other clinical factors were associated with short total PFS in the multivariable analysis.
CONCLUSIONS: Both treatment sequences are clinically feasible. A clinical benefit was noted in the sequential combination of ICIs followed by tebentafusp. This observation is limited by the retrospective nature of the study and merits further investigation in prospective clinical trials.
Recommended Citation
Dimitriou, Florentia; Orloff, Marlana; Koch Hein, Erica; Cheng, Phil; Hughes, Isaac; Simeone, Ester; Montazeri, Kamaneh; Grover, Piyush; Mehmi, Inderjit; Gerard, Camille; Gaudy-Marqueste, Caroline; Grob, Jean-Jacques; Michielin, Olivier; Hamid, Omid; Long, Georgina; Sullivan, Ryan; Kapiteijn, Ellen; Johnson, Douglas; Ascierto, Paolo; Joshua, Anthony; Carvajal, Richard; Butler, Marcus; Hassel, Jessica; and Dummer, Reinhard, "Treatment Sequence With Tebentafusp and Immune Checkpoint Inhibitors in Patients With Metastatic Uveal Melanoma and Metastatic GNA11/GNAQ Mutant Melanocytic Tumors" (2025). Kimmel Cancer Center Faculty Papers. Paper 140.
https://jdc.jefferson.edu/kimmelccfp/140
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
PubMed ID
39647344
Language
English
Included in
Amino Acids, Peptides, and Proteins Commons, Chemical Actions and Uses Commons, Diagnosis Commons, Eye Diseases Commons, Neoplasms Commons, Oncology Commons
Comments
This article is the author's final published version in European journal of cancer, Volume 214, January 2025 , Article number 115161.
The published version is available at https://doi.org/10.1016/j.ejca.2024.115161.
Copyright © 2024 The Authors