1078MO MIND-DC: A randomized phase III trial to assess the efficacy of adjuvant dendritic cell vaccination in comparison to placebo in stage IIIB and IIIC melanoma patients

Bol, Kalijn F.; Bloemendal, Martine; Willigen, Willem van; Schreibelt, Gerty; Bree, S. Hins-de; Goede, Anna de; Veldt, Astrid A.M. van der; Figdor, C.; Groot, Jan Willem B. de; Wilt, J. De; Textor, Johannes; Gerritsen, Winald R.; Vries, Jolanda De

doi:10.1016/j.annonc.2020.08.1202

Cited by 10 publications

(9 citation statements)

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“…While cancer vaccine monotherapy has been mostly ineffective, one US FDA-approved dendritic cell (DC) vaccine is available for the treatment of prostate cancer. 9 In melanoma, there has been no such success, even with DC vaccines , 10 but few trials have studied such therapy in the adjuvant setting, where we expect vaccines to have a more meaningful effect. 11 Additionally, while vaccine monotherapy may not be effective in those with intact metastatic disease, a vaccine-induced immune response may serve to improve responses to CPI therapy.…”

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confidence: 99%

A Phase IIb Randomized Controlled Trial of the TLPLDC Vaccine as Adjuvant Therapy After Surgical Resection of Stage III/IV Melanoma: A Primary Analysis

et al. 2021

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Background Melanoma therapy has changed dramatically over the last decade with improvements in immunotherapy, yet many patients do not respond to current therapies. This novel vaccine strategy may prime a patient’s immune system against their tumor and work synergistically with immunotherapy against advanced-stage melanoma. Methods This was a prospective, randomized, double-blind, placebo-controlled, phase IIb trial of the tumor lysate, particle-loaded, dendritic cell (TLPLDC) vaccine administered to prevent recurrence in patients with resected stage III/IV melanoma. Patients were enrolled and randomized 2:1 to the TLPLDC vaccine or placebo (empty yeast cell wall particles and autologous dendritic cells). Both intention-to-treat (ITT) and per treatment (PT) analyses were predefined, with PT analysis including patients who remained disease-free through the primary vaccine/placebo series (6 months). Results A total of 144 patients were randomized (103 vaccine, 41 control). Therapy was well-tolerated with similar toxicity between treatment arms; one patient in each group experienced related serious adverse events. While disease-free survival (DFS) was not different between groups in ITT analysis, in PT analysis the vaccine group showed improved 24-month DFS (62.9% vs. 34.8%, p = 0.041). Conclusions This phase IIb trial of TLPLDC vaccine administered to patients with resected stage III/IV melanoma shows TLPLDC is well-tolerated and improves DFS in patients who complete the primary vaccine series. This suggests patients who do not recur early benefit from TLPLDC in preventing future recurrence from melanoma. A phase III trial of TLPLDC + checkpoint inhibitor versus checkpoint inhibitor alone in patients with advanced, surgically resected melanoma is under development. Trial Registration NCT02301611. Supplementary information The online version contains supplementary material available at (10.1245/s10434-021-09709-1).

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confidence: 99%

A Phase IIb Randomized Controlled Trial of the TLPLDC Vaccine as Adjuvant Therapy After Surgical Resection of Stage III/IV Melanoma: A Primary Analysis

et al. 2021

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“…There were seven trials (10 arms, 7675 patients) used ICIs as experimental group; 5 , 6 , 9 - 12 , 27 – 29 three trials (four arms, 2029 patients) used targeted therapy as experimental group 13 , 30 – 32 ; 11 trials (17 arms, 5214 patients) used IFN and/or chemotherapy as experimental group; 16 , 33 - 42 and six trials (10 arms, 1791 patients) applied vaccines or/and GMCSF as experimental group. 16 – 18 , 43 – 45 All trials reported their DFS outcomes, 23 trials reported OS outcomes, and 17 trials evaluated the tolerability of therapeutic regimens. In all, 24 trials reported their median follow-up duration (ranged from 16 to 91.2 months); 10 trials reported the proportion of BRAF mutation-positive patients; five trials reported the proportion of PD-L1-positive patients.…”

Section: Resultsmentioning

confidence: 99%

“…Researchers have been trying to apply tumor vaccines to the adjuvant therapy of melanoma, and several phase II/III RCTs have evaluated the efficacy of vaccines, but all have failed. These vaccines include peptide vaccine (PV), 43 GMK vaccine (GMKV), 40 DCV, 17 and allogeneic TCV. 45 …”

Section: Discussionmentioning

confidence: 99%

“… 14 With the development of bioinformation technology and next-generation sequencing (NGS) technology, several new vaccines have been developed. In the past 2 years, three double-blinded RCTs have evaluated the efficacy and tolerability of dendritic cell-based vaccine (DCV), 15 seviprotimut-L vaccine (POL-103A), 16 and tumor lysate, particle-loaded, dendritic cell vaccine (TLPLDCV) 17 , 18 in preventing the postoperative recurrence of resected stage III melanoma.…”

Section: Introductionmentioning

confidence: 99%

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Comparison of efficacy and tolerability of adjuvant therapy for resected high-risk stage III-IV cutaneous melanoma: a systemic review and Bayesian network meta-analysis

Zhu

Zhang

et al. 2023

Ther Adv Med Oncol

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Background: Although immune checkpoint inhibitors (ICIs) and targeted therapies have been widely used as adjuvant treatment for resected melanoma, the optimal therapy remains controversial. Therefore, we conducted this updated network meta-analysis (NMA) to assess the efficacy and tolerability of adjuvant therapies for cutaneous melanoma. Methods: PubMed, Embase, Cochrane library, and Web of Science were systematically searched for relevant literatures published in the last 30 years. Disease-free survival (DFS), overall survival (OS), and serious adverse events were considered as the efficacy and tolerability outcomes. Results: In all, 27 randomized controlled trials (RCTs) including 16,709 stage III–IV melanoma patients were enrolled in this NMA. For BRAF wild-type melanoma, our analysis showed that both nivolumab and pembrolizumab demonstrated significantly better DFS and tolerability than ipilimumab (10 mg/kg). Nivolumab, pembrolizumab, ipilimumab (3 mg/kg), and ipilimumab (10 mg/kg) all appeared to be effective in prolonging OS, but no therapy demonstrated significantly better OS than ipilimumab (10 mg/kg). Nivolumab + ipilimumab showed the best DFS, but did not appear to be effective in improving OS and ranked only seventh in tolerability. Vaccines and granulocyte-macrophage colony-stimulating factor therapies were well tolerated, but all failed to improve the DFS or OS in stage III melanoma patients. In terms of BRAF mutation-positive melanoma, ICIs (nivolumab + ipilimumab, nivolumab, pembrolizumab, ipilimumab; 10 mg/kg) exhibited comparable efficacy to dabrafenib + trametinib, and all these therapies showed significantly better DFS than placebo. Conclusion: Considering efficacy and tolerability, nivolumab and pembrolizumab seem to be preferable adjuvant therapies for patients with stage III–IV melanoma. For BRAF mutation-positive patients, more RCTs are still required to determine which is better between ICIs and targeted therapy.

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“…However, accrual was stopped prematurely after inclusion of 151 patients due to the availability of adjuvant treatment with anti-PD-1 antibodies in the Netherlands since November 2018. Adjuvant nDC-vaccination in stage IIIB and IIIC melanoma patients showed no benefit over placebo in terms of 2-year recurrence-free survival [41].…”

Section: Primary Naturally Circulating Dendritic Cells: More Potent V...mentioning

confidence: 91%

Current “state of the art” on dendritic cell-based cancer vaccines in melanoma

Schwarze

Geeraerts

Tuyaerts

et al. 2023

Current Opinion in Oncology

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Purpose of review Dendritic cells (DCs) are the gatekeepers of our immune system and indispensable in the antitumor immune response. In recent years, their classification has been revised considerably using single-cell sequencing approaches. In this review, we focus on their unique role in cancer and how specific DC subsets can be manipulated to induce an effective and durable antitumor response. Recent findings Historically, due to the ease of their isolation in sufficient cell numbers from peripheral blood, the utility of monocyte-derived DCs as therapeutic cancer vaccines was explored in the clinic. However, it became clear that naturally circulating myeloid DCs (myDC), exerting their physiological role, are a functionally more powerful cellular source of antigen presenting cells. With the advent of immunomagnetic bead technology to isolate naturally circulating DC subsets, the therapeutic value of these myDC subsets is currently being explored. Since DCs are also needed in the tumor microenvironment in order to “relicense” the activity of antitumor T cells, also intratumoral administration routes for DC vaccines are explored. In addition, to circumvent the use of expensive cellular vaccines, approaches to attract DCs to the tumor microenvironment are considered of interest in order to repair a defective cancer-immunity cycle. Summary In recent years, the type of DCs used for vaccination and their administration route evolved considerably. Intratumoral vaccination strategies require combination with additional stimuli to ensure proper functioning of DCs in the tumor microenvironment. Moreover, intratumoral administration limits the applicability to patients with accessible lesions.

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1078MO MIND-DC: A randomized phase III trial to assess the efficacy of adjuvant dendritic cell vaccination in comparison to placebo in stage IIIB and IIIC melanoma patients

Cited by 10 publications

References 0 publications

A Phase IIb Randomized Controlled Trial of the TLPLDC Vaccine as Adjuvant Therapy After Surgical Resection of Stage III/IV Melanoma: A Primary Analysis

A Phase IIb Randomized Controlled Trial of the TLPLDC Vaccine as Adjuvant Therapy After Surgical Resection of Stage III/IV Melanoma: A Primary Analysis

Comparison of efficacy and tolerability of adjuvant therapy for resected high-risk stage III-IV cutaneous melanoma: a systemic review and Bayesian network meta-analysis

Current “state of the art” on dendritic cell-based cancer vaccines in melanoma

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