Impact Of Disease-Free Interval On Recurrence In High-Risk Melanoma Patients In A Phase Iib Trial Of The Tumor Lysate Particle Loaded Dendritic Cell (Tlpldc) Vaccine

Background: Immunotherapy has become a mainstay of adjuvant treatment of advanced melanoma, but recurrence rates remain high. TLPLDC is a personalized vaccine that was shown in a multi-center, double-blind, placebo-controlled phase IIb trial to be safe, well tolerated, and effective for preventing recurrence in patients with resectable stage III or IV melanoma. The trial enrolled patients who had either a new diagnosis of melanoma or recurrent disease. It is hypothesized that the length of disease-free interval (DFI) may be a marker of more indolent disease and therefore a good prognostic factor for vaccine efficacy. In this study, we examined the impact of disease-free interval on response to the vaccination. Methods: Vaccine production and dosing has been described elsewhere. Patients were characterized as having either primary or recurrent disease at the time of enrollment. For recurrent patients, DFI was defined as the length of time between their initial biopsy establishing a diagnosis of melanoma and complete surgical resection. Patients were grouped by DFI into a primary and recurrent group, where the recurrent group had DFI >3 months and the primary group had no prior disease or recurrence with DFI Results: Patients were randomized 2:1 (103 vaccine group, 41 control group) and divided into a recurrent group (n=48) and a primary group (n=96). There was no difference between groups in stage, age, margin status, BRAF mutation, or use of concurrent immunotherapy including checkpoint inhibitors. Patients in the recurrent group had numerically improved 24-month DFS with vaccine vs. placebo (52.6% vs. 23.5%, p=0.214) whereas the primary group had no difference (32.9% vs. 31.8%, p=0.451). Patients in the recurrent group had significantly improved overall survival with vaccine vs. placebo (94.4% vs. 50.5%, p=0.011) whereas the primary group had no difference (83.4% vs. 90.2%, p=0.779). Conclusions: The TLPLDC vaccine improved overall survival in patients with DFI >3 months prior to recurrence. These patients have more indolent disease biology and a less immunosuppressive tumor microenvironment, where monotherapy with a cancer vaccine is thought to be more effective. Further study is required to identify patients at initial presentation who are more likely to benefit from the TLPLDC vaccine. Meanwhile, combination therapy with vaccine and checkpoint inhibitor may be required for those with more aggressive disease biology. Citation Format: Robert Connor Chick, Phillip M. Kemp Bohan, Timothy J. Vreeland, Annelies T. Hickerson, Jessica L. Cindass, Diane F. Hale, Guy Travis Clifton, George E. Peoples. Impact of disease-free interval on recurrence in high-risk melanoma patients in a phase IIb trial of the tumor lysate particle loaded dendritic cell (TLPLDC) vaccine [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6537.