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ORIGINAL RESEARCH ARTICLE

Factors associated with response to talimogene laherparepvec in the treatment of advanced melanoma

Anupama Balasubramanian1*† ,  Michela Salusti-Simpson1† ,  Peter Callas2 ,  Conor O’Neill1,3 ,  Hibba Rehman1,4 ,  Shahid Ahmed1,4 ,  Mirabelle Sajisevi1,5 ,  Christopher J. Anker1,6 ,  Jessica Cintolo-Gonzalez1,3*
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1 Larner College of Medicine, University of Vermont, Burlington, Vermont, United States of America
2 Department of Mathematics Statistics, College of Engineering and Mathematical Sciences, University of Vermont, Burlington, Vermont, United States of America
3 Division of Surgical Oncology, Department of Surgery, University of Vermont Medical Center, Burlington, Vermont, United States of America
4 Division of Hematology/Oncology, Department of Medicine, University of Vermont Medical Center, Burlington, Vermont, United States of America
5 Division of Otolaryngology, Department of Surgery, University of Vermont Medical Center, Burlington, Vermont, United States of America
6 Division of Radiation Oncology, University of Vermont Cancer Center, Burlington, Vermont, United States of America
MI 2024, 1(1), 95–105; https://doi.org/10.36922/mi.3445
Submitted: 18 April 2024 | Accepted: 24 May 2024 | Published: 4 June 2024
© 2024 by the Author (s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

Talimogene laherparepvec (T-VEC) is currently the only United States Food and Drug Administration-approved intralesional therapy for advanced melanoma. Recent studies have assessed the integration of T-VEC with systemic immunotherapy, though the response remains variable. Therefore, we sought to identify factors associated with the response to T-VEC by conducting a retrospective, single-center analysis involving melanoma patients treated with T-VEC. In the present study, we recorded demographic and clinicopathological data, details of T-VEC treatments, prior and concurrent treatments, and clinical outcomes. The primary endpoint was the in-field overall response rate (ORR: complete + partial). Secondary endpoints included complete in-field response, defined as complete resolution of disease or a negative biopsy; disease failure-free survival (DFFS), defined from the initiation of treatment as the time to progression in patients who did not experience a disease-free interval and time to recurrence in those who did; and overall survival (OS). We used two-sample t-tests for continuous variables and Fisher’s exact test for categorical variables. DFFS and OS were further analyzed using the Kaplan–Meier method and log-rank tests for selected variables. Among the 18 patients who met the inclusion criteria, an in-field response was observed in 14 (78%) patients. Low disease burden (<5 lesions or a total diameter <5 cm) was associated with a higher in-field ORR compared to high-burden disease (100% vs. 43%, P = 0.01). There was a trend toward decreased in-field ORR for patients with >2 prior lines of systemic therapy (P = 0.18). With a median follow-up of 386 days, DFFS was associated with BRAF wild-type melanoma (P = 0.04), an in-field ORR (P = 0.007), and a measurable bystander response (P = 0.01). Two or more prior lines of immunotherapy were associated with poorer survival (P = 0.006) and worse DFFS (P = 0.02). In conclusion, despite a low sample size, we identified covariates associated with in-field ORR, DFFS, and OS, warranting further study.

Keywords
Melanoma
In-transit metastases
Intralesional therapy
Immunotherapy
Talimogene laherparepvec
Imlygic®
T-VEC
Funding
None.
Conflict of interest
The authors declare that they have no competing interests.
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Microbes & Immunity, Electronic ISSN: 3029-2883 Print ISSN: 3041-0886, Published by AccScience Publishing
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