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Clinical Trial
. 2024 Feb 23;15(1):1632.
doi: 10.1038/s41467-024-45358-0.

Adjuvant dendritic cell therapy in stage IIIB/C melanoma: the MIND-DC randomized phase III trial

Kalijn F Bol  1   2 , Gerty Schreibelt #  1 , Martine Bloemendal #  1   2 , Wouter W van Willigen #  1   2 , Simone Hins-de Bree  1 , Anna L de Goede  3 , Annemiek J de Boer  1 , Kevin J H Bos  1 , Tjitske Duiveman-de Boer  1 , Michel A M Olde Nordkamp  1 , Tom G M van Oorschot  1 , Carlijn J Popelier  1 , Jeanne M Pots  1 , Nicole M Scharenborg  1 , Mandy W M M van de Rakt  1 , Valeska de Ruiter  1 , Wilmy S van Meeteren  4 , Michelle M van Rossum  4 , Sandra J Croockewit  5 , Bouke J Koeneman  1 , Jeroen H A Creemers  1 , Inge M N Wortel  1   6 , Caroline Angerer  7 , Mareke Brüning  7 , Katja Petry  7 , Andrzej Dzionek  7 , Astrid A van der Veldt  8 , Dirk J van Grünhagen  9 , Johanna E M Werner  10 , Johannes J Bonenkamp  10 , John B A G Haanen  11 , Marye J Boers-Sonderen  2 , Rutger H T Koornstra  2 , Martijn F Boomsma  12 , Erik H J Aarntzen  13 , Martin Gotthardt  13 , James Nagarajah  13 , Theo J M de Witte  1 , Carl G Figdor  1 , Johannes H W de Wilt  10 , Johannes Textor  1   6 , Jan Willem B de Groot  14 , Winald R Gerritsen  2 , I Jolanda M de Vries  15
Affiliations
Clinical Trial

Adjuvant dendritic cell therapy in stage IIIB/C melanoma: the MIND-DC randomized phase III trial

Kalijn F Bol et al. Nat Commun. .

Abstract

Autologous natural dendritic cells (nDCs) treatment can induce tumor-specific immune responses and clinical responses in cancer patients. In this phase III clinical trial (NCT02993315), 148 patients with resected stage IIIB/C melanoma were randomized to adjuvant treatment with nDCs (n = 99) or placebo (n = 49). Active treatment consisted of intranodally injected autologous CD1c+ conventional and plasmacytoid DCs loaded with tumor antigens. The primary endpoint was the 2-year recurrence-free survival (RFS) rate, whereas the secondary endpoints included median RFS, 2-year and median overall survival, adverse event profile, and immunological response The 2-year RFS rate was 36.8% in the nDC treatment group and 46.9% in the control group (p = 0.31). Median RFS was 12.7 months vs 19.9 months, respectively (hazard ratio 1.25; 90% CI: 0.88-1.79; p = 0.29). Median overall survival was not reached in both treatment groups (hazard ratio 1.32; 90% CI: 0.73-2.38; p = 0.44). Grade 3-4 study-related adverse events occurred in 5% and 6% of patients. Functional antigen-specific T cell responses could be detected in 67.1% of patients tested in the nDC treatment group vs 3.8% of patients tested in the control group (p < 0.001). In conclusion, while adjuvant nDC treatment in stage IIIB/C melanoma patients generated specific immune responses and was well tolerated, no benefit in RFS was observed.

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Conflict of interest statement

K.F.B.: consultancy fees (all paid to institute) from MSD and Pierre Fabre. A.A.v.d.V.: consultancy fees (all paid to institute) from BMS, MSD, Pierre Fabre, Merck, Pfizer, Novartis, Sanofi, Ipsen, Eisai, Roche. CA/MBr/KP/AD: employees of Miltenyi Biotec. J.W.B.d.G.: received personal fees outside the submitted work from Bristol-Myers Squibb, Roche, Pierre Fabre, Servier, MSD, and Novartis. J.B.A.G.H.: advisory relationships with Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Celsius Therapeutics, GSK, Immunocore, Ipsen, MSD, Merck Serono, Novartis, Neon Therapeutics, Pfizer, Roche/Genentech, Sanofi, and Seattle Genetics and has received research grants not related to this paper from Novartis, BMS, MSD, and Neon Therapeutics. W.R.G.: speaker fees from MSD; advisory role (institutional) for Bristol-Myers Squibb and Bayer; research grants (institutional) from Astellas, Bayer, Janssen-Cilag, MSD. The remaining authors declare no competing interests.

Figures

Fig. 1
Fig. 1. Trial profile.
CONSORT diagram showing reasons for exclusion from the study and the number of patients included in the analyses.
Fig. 2
Fig. 2. Kaplan−Meier estimates of the survival curves of the two treatment groups.
a Recurrence-free survival and (b) overall survival. Source data are provided as a Source Data file.
Fig. 3
Fig. 3. Functional antigen-specific T cells in the immune population.
Successful T cell outgrowth from delayed-type hypersensitivity skin test biopsies for testing is shown and whether outgrown skin-test infiltrating lymphocytes produce IFNγ upon co-culture with autologous PBMCs loaded with the relevant antigens for the nDC treatment group (left) and control group (right). Source data are provided as a Source Data file.
Fig. 4
Fig. 4. Treatment schedule.
Randomized patients underwent an apheresis to harvest natural dendritic cells (nDCs). A treatment cycle consisted of 3 nDC injections or placebo injections. The first cycle was followed by a delayed-type hypersensitivity (DTH) skin test including skin biopsies 2 days later. Patients were assessed for recurrence of disease with CT scans.
See this image and copyright information in PMC

References

    1. Banchereau J, Steinman RM. Dendritic cells and the control of immunity. Nature. 1998;392:245–252. doi: 10.1038/32588. - DOI - PubMed
    1. Palucka K, Banchereau J. Cancer immunotherapy via dendritic cells. Nat. Rev. Cancer. 2012;12:265–277. doi: 10.1038/nrc3258. - DOI - PMC - PubMed
    1. Baraibar I, Melero I, Ponz-Sarvise M, Castanon E. Safety and tolerability of immune checkpoint inhibitors (PD-1 and PD-L1) in Cancer. Drug Saf. 2019;42:281–294. doi: 10.1007/s40264-018-0774-8. - DOI - PubMed
    1. Anguille S, Smits EL, Lion E, van Tendeloo VF, Berneman ZN. Clinical use of dendritic cells for cancer therapy. Lancet Oncol. 2014;15:e257–e267. doi: 10.1016/S1470-2045(13)70585-0. - DOI - PubMed
    1. Soruri A, et al. IL-4 down-regulates anaphylatoxin receptors in monocytes and dendritic cells and impairs anaphylatoxin-induced migration in vivo. J. Immunol. 2003;170:3306–3314. doi: 10.4049/jimmunol.170.6.3306. - DOI - PubMed

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