Multi‐institutional, prospective, randomized, double‐blind, placebo‐controlled phase IIb trial of the tumor lysate, particle‐loaded, dendritic cell (TLPLDC) vaccine to prevent recurrence in high‐risk melanoma patients: A subgroup analysis

• Published in: Cancer medicine (Malden, MA) Vol. 10; no. 13; pp. 4302 - 4311
• Main Authors: Chick, Robert C., Faries, Mark B., Hale, Diane F., Kemp Bohan, Phillip M, Hickerson, Annelies T., Vreeland, Timothy J., Myers, John W., Cindass, Jessica L., Brown, Tommy A., Hyngstrom, John, Berger, Adam C., Jakub, James W., Sussman, Jeffrey J., Shaheen, Montaser, Clifton, Guy T., Park, Hyohyun, Sloan, Amanda J., Wagner, Thomas, Peoples, George E.
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01-07-2021; John Wiley and Sons Inc; Wiley
• Subjects: Aged; Cancer therapies; cancer vaccine; Cancer vaccines; Cancer Vaccines - therapeutic use; Clinical Cancer Research; Dendritic cells; Dendritic Cells - immunology; Disease-Free Survival; Double-Blind Method; Double-blind studies; Humans; Immune checkpoint; Immune Checkpoint Inhibitors - therapeutic use; Immunotherapy; Immunotherapy, Adoptive - methods; Melanoma; Melanoma - mortality; Melanoma - pathology; Melanoma - surgery; Melanoma - therapy; Metastasis; Middle Aged; Neoplasm Recurrence, Local - mortality; Neoplasm Recurrence, Local - prevention & control; Neoplasm Staging; Original Research; Patients; personalized medicine; Placebos; Placebos - therapeutic use; Population; Precision Medicine; Prospective Studies; Skin Neoplasms - mortality; Skin Neoplasms - pathology; Skin Neoplasms - surgery; Skin Neoplasms - therapy; Surgery; Survival analysis; Vaccines; melanoma; cancer vaccine; immunotherapy; personalized medicine
• ISSN: 2045-7634; 2045-7634
• DOI: 10.1002/cam4.3969

Background
Checkpoint inhibitors (CPI) in combination with cell‐based vaccines may produce synergistic antitumor immunity. The primary analysis of the randomized and blinded phase IIb trial in resected stage III/IV melanoma demonstrated TLPLDC is safe and improved 24‐month disease‐free survival (DFS) in the per treatment (PT) analysis. Here, we examine efficacy within pre‐specified and exploratory subgroups.
Methods
Stage III/IV patients rendered disease‐free by surgery were randomized 2:1 to TLPLDC vaccine versus placebo. The pre‐specified PT analysis included only patients completing the primary vaccine/placebo series at 6 months. Kaplan–Meier analysis was used to compare 24‐month DFS among subgroups.
Results
There were no clinicopathologic differences between subgroups except stage IV patients were more likely to receive CPI. In stage IV patients, 24‐month DFS was 43% for vaccine versus 0% for placebo (p = 0.098) in the ITT analysis and 73% versus 0% (p = 0.002) in the PT analysis. There was no significant difference in 24‐month DFS when stratified by use of immunotherapy or CPI. For patients with resected recurrent disease, 24‐month DFS was 88.9% versus 33.3% (p = 0.013) in the PT analysis. All benefit from vaccination was in the PT analysis; no benefit was found in patients receiving up to three doses.
Conclusion
The TLPLDC vaccine improved DFS in patients completing the primary vaccine series, particularly in the resected stage IV patients. The efficacy of the TLPLDC vaccine will be confirmed in a phase III study evaluating adjuvant TLPLDC + CPI versus Placebo + CPI in resected stage IV melanoma patients.
TLPLDC is an autologous tumor lysate vaccine made with autologous dendritic cells to prevent recurrence in patients with high‐risk resected melanoma. In this analysis, the vaccine was found to have the most benefit in stage IV resected patients and may have a synergistic effect in combination with checkpoint inhibitors.
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