Safety and efficacy of autologous tumor lysate particleloaded dendritic cell vaccination in combination with systemic therapies in patients with recurrent and metastatic melanoma

Alexandra M. Adams, Robert C. Chick, Timothy J. Vreeland, Guy T. Clifton, Diane F. Hale, Patrick M. McCarthy, Anne E. O'Shea, Phillip M.Kemp Bohan, Annelies T. Hickerson, Hyohyun Park, Amanda Jo Ellen Sloan, John Hyngstrom, Adam C. Berger, James W. Jakub, Jeffrey J. Sussman, Montaser Shaheen, Thomas Wagner, Mark B. Faries, George E. Peoples

Research output: Contribution to journalArticlepeer-review

Abstract

Immunotherapy has revolutionized the treatment of melanoma, yet survival remains poor for patients with metastatic disease. The autologous tumor lysate, particleloaded, dendritic cell (TLPLDC) vaccine has been shown to be safe adjuvant therapy for patients with resected stage III/IV melanoma who complete the primary vaccine series. Here, we describe an open-label trial of patients with metastatic melanoma treated with TLPLDC vaccine in addition to standard of care (SoC) therapies. The TLPLDC vaccine is created by loading autologous tumor lysate into yeast cell wall particles, which are phagocytosed by autologous dendritic cells ex vivo. Patients who recurred while enrolled in a phase IIb trial of adjuvant TLPLDC vaccine (crossover cohort) and patients with measurable metastatic melanoma cohort were offered TLPLDC vaccine along with SoC therapies. Tumor response was measured by RECIST 1.1 criteria. Overall survival (OS) and progression-free survival (PFS) were estimated by intention-to-treat analysis. Fifty-four patients were enrolled (28 in crossover cohort; 26 in metastatic melanoma cohort). The vaccine was well-tolerated with no grade ≥3 adverse events when given with SoC therapies to include checkpoint inhibitors, BRAF/MEK inhibitors, tyrosine kinase inhibitors, intralesional therapy and/or radiation. In the crossover arm, OS was 76.5% and PFS was 57.1% (median follow-up of 13.9 months). In the metastatic melanoma arm, OS was 85.7% and PFS was 52.2% (median follow-up 8.5 months). The TLPLDC vaccine is well-tolerated and safe in combination with SoC therapies. Future trials will determine the efficacy of TLPLDC in combination with SoC therapies in metastatic melanoma.

Original languageEnglish (US)
Pages (from-to)378-388
Number of pages11
JournalMelanoma Research
DOIs
StateAccepted/In press - 2021

Keywords

  • Cancer vaccine
  • Immunotherapy
  • Melanoma
  • Personalized vaccine

ASJC Scopus subject areas

  • Oncology
  • Dermatology
  • Cancer Research

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