{"doi":"10.1136/jitc-2025-013564","title":"Real-world outcomes of talimogene laherparepvec as salvage therapy for advanced melanoma","abstract":"BACKGROUND: Talimogene laherparepvec (T-VEC) is an oncolytic herpes simplex virus therapy approved for treatment of unresectable and metastatic melanoma. However, real-world use often occurs in heavily pretreated patients, where evidence of effectiveness remains limited. This study evaluates treatment responses and clinical factors influencing T-VEC outcomes in patients with diverse treatment histories. METHODS: We analyzed patients with metastatic melanoma treated with T-VEC between 2015 and 2024. Objective responses (OR), complete response (CR) and partial response were assessed using univariate and multivariate Cox regression models. Durability of responses, progression-free survival (PFS), and overall survival (OS) were evaluated using Kaplan-Meier estimates. RESULTS: Among 121 patients, 105 (87%) patients received ≥1 prior lines of systemic therapy; 48 (40%) had a current or prior history of distant metastatic disease, and 42 (35%) had both injectable and non-injectable disease at the T-VEC initiation. Median PFS was 12.2 months (95% CI 6.2 to 20.9), and median OS was 35.5 months (95% CI 25.8 to 63.9). Of 113 evaluable patients, 76 (67%, 95% CI 58% to 76%) achieved an OR, including 39 (35%, 95% CI 26% to 44%) CR. The probability OR by 6 months was 56% (95% CI 46% to 65%). Of the 39 patients achieving CR, 37 (95%) remained alive and progression-free at last follow-up (median 19.1 months). In multivariate analysis, the adjusted HR (aHR) for OR in patients with non-injectable distant metastases at T-VEC initiation relative to those without was 0.43 (95% CI 0.23 to 0.78; p=0.006). The aHR for OR among those immunosuppressed compared with those not immunosuppressed was 0.18 (95% CI 0.04 to 0.69; p=0.013), indicating a reduced likelihood of response for patients who were immunosuppressed. Unadjusted HRs for achieving an OR after 1, 2, and ≥3 prior therapies (vs none) were 1.20 (95% CI 0.57 to 2.52; p=0.627), 1.21 (95% CI 0.52 to 2.80; p=0.653), and 0.77 (95% CI 0.35 to 1.68; p=0.507), respectively. CONCLUSIONS: This study demonstrates T-VEC's potential efficacy in achieving meaningful disease control and response durability in patients with unresectable and/or metastatic melanoma, including those with diverse prior-treatment histories and comorbidities.","journal":"Journal for ImmunoTherapy of Cancer","year":2025,"id":529635,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9403,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1408967,"name":"Smitha Chandrasekhar","orcid":null,"position":1,"is_corresponding":false},{"id":236737,"name":"Ted Gooley","orcid":"0000-0002-8182-3652","position":2,"is_corresponding":false},{"id":106500,"name":"Rita E. Chen","orcid":"0000-0002-5100-7750","position":3,"is_corresponding":false},{"id":985879,"name":"Coley Doolittle‐Amieva","orcid":null,"position":4,"is_corresponding":false},{"id":883434,"name":"George Ansstas","orcid":"0000-0002-7178-8777","position":5,"is_corresponding":false},{"id":230463,"name":"Shailender Bhatia","orcid":"0000-0002-3816-2238","position":6,"is_corresponding":false},{"id":801030,"name":"Evan Hall","orcid":"0000-0002-0305-7745","position":7,"is_corresponding":false},{"id":1408968,"name":"Paul T Nghiem","orcid":null,"position":8,"is_corresponding":false},{"id":285792,"name":"Song Y. Park","orcid":"0000-0003-4366-1821","position":9,"is_corresponding":false},{"id":110548,"name":"David Y. Chen","orcid":"0000-0002-3681-6576","position":10,"is_corresponding":false},{"id":1408966,"name":"Melissa M Yamada","orcid":null,"position":0,"is_corresponding":true}],"reference_count":33,"raw_metadata":null,"created_at":"2026-07-19T02:50:56.971987Z","pmid":"41448830","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}