Retrospective study of unresectable stage III or stage IV melanoma refractory to immune checkpoint and BRAF/MEK inhibitors, treated with triplet vs doublet therapy: A single institution experience.

Abstract

e21500 Background: The incidence of melanoma has been increasing in the last decade. Advanced malignant melanoma (unresectable stage III or stage IV melanoma) is primarily treated with either immune checkpoint inhibitors and/or BRAF/MEK inhibitors if BRAF V600E mutation is positive in tumor tissue 1,2 . T-VEC (Talimogene Laherparepvec) is a genetically engineered attenuated oncolytic herpes simplex virus-1 that is approved for the treatment of advanced melanoma 3 . To the best of our knowledge, there are no clinical trials or real-world studies that compare combined modalities of immunotherapy, SBRT (Stereotactic Body radiation Treatment), and TVEC. We did a retrospective analysis in patients comparing triplet therapy (TVEC, SBRT, and immunotherapy) with doublet therapy (combination therapy with either TVEC and immunotherapy or TVEC and SBRT). Methods: We performed a retrospective analysis of patients who received TVEC treatment at Lehigh Valley Hospital Network (LVHN), Allentown, Pennsylvania between Jan 1, 2015, to Dec 31, 2023. A total of 35 patients (ranging from 25 to 90 years old) made up our study population, with 16 patients receiving triplet therapy, and 19 receiving doublet therapy (out of which 2 patients received TVEC and SBRT, and 17 received TVEC and immunotherapy). Our institution’s electronic medical record (EMR) was used to collect patients’ data. Log-rank test was then used to analyze the Overall Survival (OS) and Progression-Free Survival (PFS) among treatment groups. Results: Overall, 65.71% of our total study population responded to treatment, with 40% of patients having a complete response. The median OS for the triplet therapy group was 11.8 months and 21.1. months in doublet therapy arm (p=0.8143). The median PFS in the triplet therapy group was 7.5 months and 10.8 months in doublet therapy arm (p=0.5848). Objective response rate (ORR) is 62.5% in triplet group and 68.4% in doublet group. All grade immune related side effects in triplet and doublet arm were 56.3% and 10.5% respectively and were mainly grade 1-2. Conclusions: Our single institution experience shows that the mOS in triplet therapy is 11.8 months and 21.1. months in doublet therapy arm (p=0.8143). mPFS in triplet and doublet therapy arm is 7.5 months and 10.8 months respectively. Objective response rate (ORR) is 62.5% in triplet group and 68.4% in doublet group and ORR is much higher compared to modern therapy trials 4,5. Patients in the triplet therapy group had a higher volume of disease which could have contributed to the decreased overall survival findings and further prospective studies are needed in this space. Triplet therapy is an option for patients with high volume disease and it was well tolerated in our patients. Limitations include retrospective nature of study, small patients volume and single institution experience.