Search

Your search keyword '"van den Eertwegh, Alfons J. M."' showing total 201 results
Start Over Author "van den Eertwegh, Alfons J. M." Search Limiters Available in Library Collection
201 results on '"van den Eertwegh, Alfons J. M."'

1. Multi-omic analysis identifies hypoalbuminemia as independent biomarker of poor outcome upon PD-1 blockade in metastatic melanoma

Author

Leek, Lindsay V. M., Notohardjo, Jessica C. L., de Joode, Karlijn, Velker, Eline L., Haanen, John B. A. G., Suijkerbuijk, Karijn P. M., Aarts, Maureen J. B., de Groot, Jan Willem B., Kapiteijn, Ellen, van den Berkmortel, Franchette W. P. J., Westgeest, Hans M., de Gruijl, Tanja D., Retel, Valesca P., Cuppen, Edwin, van der Veldt, Astrid A. M., Labots, Mariette, Voest, Emile E., van de Haar, Joris, and van den Eertwegh, Alfons J. M.

Published
2024
Full Text
View/download PDF

2. Selective tumor antigen vaccine delivery to human CD169+ antigen-presenting cells using ganglioside-liposomes

Author

Affandi, Alsya J., Grabowska, Joanna, Olesek, Katarzyna, Venegas, Miguel Lopez, Barbaria, Arnaud, Rodríguez, Ernesto, Mulder, Patrick P. G., Pijffers, Helen J., Ambrosini, Martino, Kalay, Hakan, O’Toole, Tom, Zwart, Eline S., Kazemier, Geert, Nazmi, Kamran, Bikker, Floris J., Stöckl, Johannes, van den Eertwegh, Alfons J. M., de Gruijl, Tanja D., Storm, Gert, van Kooyk, Yvette, and den Haan, Joke M. M.

Published
2020

3. Multi-omic analysis identifies hypoalbuminemia as independent biomarker of poor outcome upon PD-1 blockade in metastatic melanoma

Author

MS Medische Oncologie, Cancer, Infection & Immunity, CMM Groep Van Mil, Leek, Lindsay V M, Notohardjo, Jessica C L, de Joode, Karlijn, Velker, Eline L, Haanen, John B A G, Suijkerbuijk, Karijn P M, Aarts, Maureen J B, de Groot, Jan Willem B, Kapiteijn, Ellen, van den Berkmortel, Franchette W P J, Westgeest, Hans M, de Gruijl, Tanja D, Retel, Valesca P, Cuppen, Edwin, van der Veldt, Astrid A M, Labots, Mariette, Voest, Emile E, van de Haar, Joris, van den Eertwegh, Alfons J M, MS Medische Oncologie, Cancer, Infection & Immunity, CMM Groep Van Mil, Leek, Lindsay V M, Notohardjo, Jessica C L, de Joode, Karlijn, Velker, Eline L, Haanen, John B A G, Suijkerbuijk, Karijn P M, Aarts, Maureen J B, de Groot, Jan Willem B, Kapiteijn, Ellen, van den Berkmortel, Franchette W P J, Westgeest, Hans M, de Gruijl, Tanja D, Retel, Valesca P, Cuppen, Edwin, van der Veldt, Astrid A M, Labots, Mariette, Voest, Emile E, van de Haar, Joris, and van den Eertwegh, Alfons J M

Published
2024

4. The Predictive Value of FDG PET/CT for Determining Progression-Free Survival in Advanced Stage III-IV BRAF-Mutated Melanoma Patients Treated With Targeted Therapy-What Can Be Learned From Progression?

Author

MS Medische Oncologie, Brain, Cancer, van der Hiel, Bernies, Aalbersberg, Else A, van den Eertwegh, Alfons J M, de Wit-van der Veen, Linda J, Stokkel, Marcel P M, Lopez-Yurda, Marta, Boellaard, Ronald, Kapiteijn, Ellen W, Hospers, Geke A P, Aarts, Maureen J B, de Vos, Filip Y F L, Boers-Sonderen, Marye J, van der Veldt, Astrid A M, de Groot, Jan Willem B, Haanen, John B A G, MS Medische Oncologie, Brain, Cancer, van der Hiel, Bernies, Aalbersberg, Else A, van den Eertwegh, Alfons J M, de Wit-van der Veen, Linda J, Stokkel, Marcel P M, Lopez-Yurda, Marta, Boellaard, Ronald, Kapiteijn, Ellen W, Hospers, Geke A P, Aarts, Maureen J B, de Vos, Filip Y F L, Boers-Sonderen, Marye J, van der Veldt, Astrid A M, de Groot, Jan Willem B, and Haanen, John B A G

Published
2024

5. BRAF/MEK inhibitor rechallenge in advanced melanoma patients

Author

Cancer, MS Medische Oncologie, Pathologie Pathologen staf, Infection & Immunity, Van Not, Olivier J, van den Eertwegh, Alfons J M, Haanen, John B, van Rijn, Rozemarijn S, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, Blank, Christian U, Boers-Sonderen, Marye J, de Groot, Jan Willem W B, Hospers, Geke AP, Kapiteijn, Ellen, Bloem, Manja, Piersma, Djura, Stevense-den Boer, Marion, Verheijden, Rik J, van der Veldt, Astrid A M, Wouters, Michel W J M, Blokx, Willeke A M, Suijkerbuijk, Karijn P M, Cancer, MS Medische Oncologie, Pathologie Pathologen staf, Infection & Immunity, Van Not, Olivier J, van den Eertwegh, Alfons J M, Haanen, John B, van Rijn, Rozemarijn S, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, Blank, Christian U, Boers-Sonderen, Marye J, de Groot, Jan Willem W B, Hospers, Geke AP, Kapiteijn, Ellen, Bloem, Manja, Piersma, Djura, Stevense-den Boer, Marion, Verheijden, Rik J, van der Veldt, Astrid A M, Wouters, Michel W J M, Blokx, Willeke A M, and Suijkerbuijk, Karijn P M

Published
2024

6. Improving survival in advanced melanoma patients: a trend analysis from 2013 to 2021

Author

Cancer, MS Medische Oncologie, Pathologie Pathologen staf, Infection & Immunity, van Not, Olivier J, van den Eertwegh, Alfons J M, Haanen, John B, Blank, Christian U, Aarts, Maureen J B, van Breeschoten, Jesper, van den Berkmortel, Franchette W P J, de Groot, Jan-Willem B, Hospers, Geke A P, Ismail, Rawa K, Kapiteijn, Ellen, Bloem, Manja, De Meza, Melissa M, Piersma, Djura, van Rijn, Rozemarijn S, Stevense-den Boer, Marion A M, van der Veldt, Astrid A M, Vreugdenhil, Gerard, Boers-Sonderen, Marye J, Blokx, Willeke A M, Wouters, Michel W J M, Suijkerbuijk, Karijn P M, Cancer, MS Medische Oncologie, Pathologie Pathologen staf, Infection & Immunity, van Not, Olivier J, van den Eertwegh, Alfons J M, Haanen, John B, Blank, Christian U, Aarts, Maureen J B, van Breeschoten, Jesper, van den Berkmortel, Franchette W P J, de Groot, Jan-Willem B, Hospers, Geke A P, Ismail, Rawa K, Kapiteijn, Ellen, Bloem, Manja, De Meza, Melissa M, Piersma, Djura, van Rijn, Rozemarijn S, Stevense-den Boer, Marion A M, van der Veldt, Astrid A M, Vreugdenhil, Gerard, Boers-Sonderen, Marye J, Blokx, Willeke A M, Wouters, Michel W J M, and Suijkerbuijk, Karijn P M

Published
2024

7. Baseline biomarkers of efficacy and on-treatment immune-profile changes associated with bempegaldesleukin plus nivolumab.

Author

Gogas, Helen, Ravimohan, Shruthi, Datta, Antara, Chhibber, Aparna, Couselo, Eva Muñoz, Diab, Adi, Pereira, Caio, Quéreux, Gaëlle, Sandhu, Shahneen, Curti, Brendan, Khushalani, Nikhil I., Taylor, Matthew H., Daniels, Gregory A., Spreafico, Anna, Meniawy, Tarek, Van Den Eertwegh, Alfons J. M., Sun, Yongliang, Arriaga, Yull, Zhou, Ming, and Long, Georgina V.

Subjects
REGULATORY T cells, TUMOR markers, NIVOLUMAB, BIOMARKERS, T cells
Abstract

In PIVOT IO 001 (NCT03635983), the combination of the investigational interleukin-2 agonist bempegaldesleukin (BEMPEG) with nivolumab (NIVO) had no added clinical benefit over NIVO monotherapy in unresectable/metastatic melanoma. Pre-defined baseline and on-treatment changes in selected biomarkers were analyzed to explore the potential mechanisms underlying the clinical observations. In each treatment arm, higher baseline tumor mutational burden or immune infiltration/inflammation was associated with improved efficacy compared with lower levels. On-treatment peripheral biomarker changes showed that BEMPEG + NIVO increased all immune cell subset counts interrogated, including regulatory T cells. This was followed by attenuation of the increase in CD8 + T cells, conventional CD4 + T cells, and systemic interferon gamma levels at later treatment cycles in the combination arm. Changes in tumor biomarkers were comparable between arms. These biomarker results help provide a better understanding of the mechanism of action of BEMPEG + NIVO and may help contextualize the clinical observations from PIVOT IO 001. [ABSTRACT FROM AUTHOR]

Published
2024
Full Text
View/download PDF

8. Response to checkpoint inhibition and targeted therapy in melanoma patients with concurrent haematological malignancies

Author

Van Not, Olivier J, van den Eertwegh, Alfons J M, Haanen, John B, van Rijn, Rozemarijn S, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, Blank, Christian U, Boers-Sonderen, Marye J, van Eijs, Mick J M, de Groot, Jan-Willem B, Hospers, Geke A P, Kapiteijn, Ellen, de Meza, Melissa, Piersma, Djura, Stevense-den Boer, Marion, van der Veldt, Astrid A M, Vreugdenhil, Gerard, Wouters, Michel W J M, Suijkerbuijk, Karijn P M, Blokx, Willeke A M, Medical Oncology, Erasmus MC other, Internal medicine, Medical oncology, AII - Cancer immunology, CCA - Cancer Treatment and quality of life, CCA - Cancer biology and immunology, Obstetrics and gynaecology, Amsterdam Reproduction & Development (AR&D), RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, Interne Geneeskunde, MUMC+: MA Medische Oncologie (9), and Guided Treatment in Optimal Selected Cancer Patients (GUTS)

Subjects
Cancer Research, OUTCOMES, Survival, CANCERS, CHRONIC LYMPHOCYTIC-LEUKEMIA, Response, Haematologic malignancy, SOLID TUMORS, Healthcare improvement science Radboud Institute for Health Sciences [Radboudumc 18], Immune checkpoint inhibitors, All institutes and research themes of the Radboud University Medical Center, SDG 3 - Good Health and Well-being, Oncology, CELLS, IMMUNOTHERAPY, Melanoma
Abstract

Background: Patients diagnosed with haematologic malignancies (HMs) have a higher risk of developing subsequent solid tumours, such as melanoma. Patients with HM were mostly excluded from clinical trials but potentially derive less benefit from immune checkpoint inhibitors (ICIs) due to disease-or treatment-related T-or B-cell dysfunction.Methods: All advanced melanoma patients treated with anti-PD-1-based treatment or tar-geted therapy between 2015 and 2021 were included from the prospective nationwide Dutch Melanoma Treatment Registry. Progression-free survival (PFS) and melanoma-specific sur-vival (MSS) were analysed for patients with HM (HM+) and without HM (HM-). A cox model was used to account for confounders associated with PFS and MSS.Results: In total, 4638 advanced melanoma patients received first-line anti-PD-1 mono -therapy (n = 1763), ipilimumab-nivolumab (n = 800), or BRAF(/MEK) inhibitors (n = 2075). Concurrent HMs were present for 46 anti-PD1-treated patients, 11 ipilimumab-nivolumab-treated patients and 43 BRAF(/MEK)-inhibitor-treated patients. In anti-PD-1-treated pa-tients, the median PFS was 2.8 months for HM+ and 9.9 months for HM- (p = 0.01). MSS was 41.2 months for HM+ and 58.1 months for HM- (p = 0.00086). In multivariable analysis, the presence of an HM was significantly associated with higher risk of melanoma progression (HRadj 1.62; 95% confidence interval [95% CI] 1.15-2.29; p = 0.006) and melanoma-related death (HRadj 1.74; 95% CI 1.09-2.78; p = 0.020). Median PFS and MSS for first-line BRAF (/MEK-) inhibitor-treated HM+ and HM- patients were not significantly different.Conclusions: Patients with HM and advanced melanoma show significantly worse melanoma -related outcomes when treated with ICI, but not targeted therapy, compared to patients without HM. Clinicians should be aware of potentially altered effectiveness of ICI in patients with active HM.(c) 2023 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Published
2023

10. Adjuvant treatment of in-transit melanoma:Narrowing the knowledge gap left by clinical trials

Author

de Meza, Melissa M, Blokx, Willeke A M, Bonenkamp, Han J, Blank, Cristian U, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, Boers-Sonderen, Marye J, de Groot, Jan Willem B, Haanen, John B, Hospers, Geke A P, Kapiteijn, Ellen W, van Not, Olivier J, Piersma, Djura, van Rijn, Rozemarijn S, Stevense-Den Boer, Marion A, van der Veldt, Astrid A M, Vreugdenhil, Gerard, van den Eertwegh, Alfons J M, Suijkerbuijk, Karijn P M, Wouters, Michel W J M, de Meza, Melissa M, Blokx, Willeke A M, Bonenkamp, Han J, Blank, Cristian U, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, Boers-Sonderen, Marye J, de Groot, Jan Willem B, Haanen, John B, Hospers, Geke A P, Kapiteijn, Ellen W, van Not, Olivier J, Piersma, Djura, van Rijn, Rozemarijn S, Stevense-Den Boer, Marion A, van der Veldt, Astrid A M, Vreugdenhil, Gerard, van den Eertwegh, Alfons J M, Suijkerbuijk, Karijn P M, and Wouters, Michel W J M

Abstract

Few clinical trials address efficacy of adjuvant systemic treatment in patients with in-transit melanoma (ITM). This study describes adjuvant systemic therapy of ITM patients beyond clinical trials. In this study, we included stage III adjuvant-treated melanoma patients registered in the nationwide Dutch Melanoma Treatment Registry between July 2018 and December 2020. Patients were divided into three groups: nodal disease only, ITM only and ITM and nodal disease. Recurrence patterns, recurrence-free survival (RFS) and overall survival (OS) at 12-months were analyzed. In our study population of 1037 patients, 66.8% had nodal disease only, 16.7% had ITM only and 16.2% had ITM with nodal disease. RFS at 12-months was comparable in the nodal only and ITM only group (72.2% vs70.1%, P = .97) but lower in ITM and nodal disease patients (57.8%; P = .01, P < .01). Locoregional metastases occurred as first recurrence in 38.9% nodal disease only, 71.9% of ITM-only and 44.0% of ITM and nodal disease patients. Distant recurrences occurred in 42.3%, 18.8% and 36.0%, respectively (P = .02). 12-months OS was not significantly different for nodal disease only patients compared with ITM-only (94.4% vs 97.6%, P = .06) but was significantly higher for ITM-only compared with ITM and nodal disease patients (97.6% vs 91.0%, P < .01). In conclusion, we showed that in the adjuvant setting, RFS rates in ITM-only patients are similar to non-ITM, though better than in ITM and nodal disease patients. Adjuvant-treated ITM-only patients less often experience distant recurrences and have a superior OS compared with ITM and nodal disease patients.

Published
2023

11. Real-world Outcomes of Ipilimumab Plus Nivolumab Combination Therapy in a Nation-wide Cohort of Advanced Melanoma Patients in the Netherlands

Author

MS Medische Oncologie, Cancer, Infection & Immunity, van Zeijl, Michiel C T, van Breeschoten, Jesper, de Wreede, Liesbeth C, Wouters, Michel W J M, Hilarius, Doranne L, Blank, Christian U, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, de Groot, Jan Willem B, Hospers, Geke A P, Kapiteijn, Ellen, Piersma, Djura, van Rijn, Rozemarijn S, Stevense-den Boer, Marion A, van der Veldt, Astrid A M, Vreugdenhil, Gerard, Boers-Sonderen, Marye J, Suijkerbuijk, Karijn P M, Haanen, John B A G, van den Eertwegh, Alfons J M, MS Medische Oncologie, Cancer, Infection & Immunity, van Zeijl, Michiel C T, van Breeschoten, Jesper, de Wreede, Liesbeth C, Wouters, Michel W J M, Hilarius, Doranne L, Blank, Christian U, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, de Groot, Jan Willem B, Hospers, Geke A P, Kapiteijn, Ellen, Piersma, Djura, van Rijn, Rozemarijn S, Stevense-den Boer, Marion A, van der Veldt, Astrid A M, Vreugdenhil, Gerard, Boers-Sonderen, Marye J, Suijkerbuijk, Karijn P M, Haanen, John B A G, and van den Eertwegh, Alfons J M

Published
2023

12. Response to checkpoint inhibition and targeted therapy in melanoma patients with concurrent haematological malignancies

Author

MS Medische Oncologie, Cancer, Infection & Immunity, Pathologie Pathologen staf, Van Not, Olivier J, van den Eertwegh, Alfons J M, Haanen, John B, van Rijn, Rozemarijn S, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, Blank, Christian U, Boers-Sonderen, Marye J, van Eijs, Mick J M, de Groot, Jan-Willem B, Hospers, Geke A P, Kapiteijn, Ellen, de Meza, Melissa, Piersma, Djura, Stevense-den Boer, Marion, van der Veldt, Astrid A M, Vreugdenhil, Gerard, Wouters, Michel W J M, Suijkerbuijk, Karijn P M, Blokx, Willeke A M, MS Medische Oncologie, Cancer, Infection & Immunity, Pathologie Pathologen staf, Van Not, Olivier J, van den Eertwegh, Alfons J M, Haanen, John B, van Rijn, Rozemarijn S, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, Blank, Christian U, Boers-Sonderen, Marye J, van Eijs, Mick J M, de Groot, Jan-Willem B, Hospers, Geke A P, Kapiteijn, Ellen, de Meza, Melissa, Piersma, Djura, Stevense-den Boer, Marion, van der Veldt, Astrid A M, Vreugdenhil, Gerard, Wouters, Michel W J M, Suijkerbuijk, Karijn P M, and Blokx, Willeke A M

Published
2023

13. Adjuvant Treatment of In-Transit Melanoma: Narrowing the Knowledge Gap Left by Clinical Trials

Author

Pathologie Pathologen staf, Cancer, MS Medische Oncologie, Infection & Immunity, de Meza, Melissa M, Blokx, Willeke A M, Bonenkamp, Han J, Blank, Cristian U, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, Boers-Sonderen, Marye J, de Groot, Jan Willem B, Haanen, John B, Hospers, Geke A P, Kapiteijn, Ellen W, van Not, Olivier J, Piersma, Djura, van Rijn, Rozemarijn S, Stevense-den Boer, Marion A, van der Veldt, Astrid A M, Vreugdenhil, Gerard, van den Eertwegh, Alfons J M, Suijkerbuijk, Karijn P M, Wouters, Michel W J M, Pathologie Pathologen staf, Cancer, MS Medische Oncologie, Infection & Immunity, de Meza, Melissa M, Blokx, Willeke A M, Bonenkamp, Han J, Blank, Cristian U, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, Boers-Sonderen, Marye J, de Groot, Jan Willem B, Haanen, John B, Hospers, Geke A P, Kapiteijn, Ellen W, van Not, Olivier J, Piersma, Djura, van Rijn, Rozemarijn S, Stevense-den Boer, Marion A, van der Veldt, Astrid A M, Vreugdenhil, Gerard, van den Eertwegh, Alfons J M, Suijkerbuijk, Karijn P M, and Wouters, Michel W J M

Published
2023

14. ASO Visual Abstract: Is a History of Optimal Staging by SLNB in the Era Prior to Adjuvant Therapy Associated with Improved Outcome Once Melanoma Patients have Progressed to Advanced Disease?

Author

Pathologie Pathologen staf, Cancer, MS Medische Oncologie, Infection & Immunity, Blankenstein, Stephanie A, Bonenkamp, Johannes J, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, Blank, Christian U, Blokx, Willeke A M, Boers-Sonderen, Marye J, van den Eertwegh, Alfons J M, Franken, Margreet G, de Groot, Jan Willem B, Haanen, John B A G, Hospers, Geke A P, Kapiteijn, Ellen W, van Not, Olivier J, Piersma, Djura, van Rijn, Rozemarijn S, Suijkerbuijk, Karijn P M, van der Veldt, Astrid A M, Vreugdenhil, Gerard, Westgeest, Hans M, Wouters, Michel W J M, van Akkooi, Alexander C J, Pathologie Pathologen staf, Cancer, MS Medische Oncologie, Infection & Immunity, Blankenstein, Stephanie A, Bonenkamp, Johannes J, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, Blank, Christian U, Blokx, Willeke A M, Boers-Sonderen, Marye J, van den Eertwegh, Alfons J M, Franken, Margreet G, de Groot, Jan Willem B, Haanen, John B A G, Hospers, Geke A P, Kapiteijn, Ellen W, van Not, Olivier J, Piersma, Djura, van Rijn, Rozemarijn S, Suijkerbuijk, Karijn P M, van der Veldt, Astrid A M, Vreugdenhil, Gerard, Westgeest, Hans M, Wouters, Michel W J M, and van Akkooi, Alexander C J

Published
2023

15. Is a History of Optimal Staging by Sentinel Lymph Node Biopsy in the Era Prior to Adjuvant Therapy Associated with Improved Outcome Once Melanoma Patients have Progressed to Advanced Disease?

Author

Pathologie Pathologen staf, Cancer, MS Medische Oncologie, Infection & Immunity, Blankenstein, Stephanie A, Bonenkamp, Johannes J, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, Blank, Christian U, Blokx, Willeke A M, Boers-Sonderen, Marye J, van den Eertwegh, Alfons J M, Franken, Margreet G, de Groot, Jan Willem B, Haanen, John B A G, Hospers, Geke A P, Kapiteijn, Ellen W, van Not, Olivier J, Piersma, Djura, van Rijn, Rozemarijn S, Suijkerbuijk, Karijn P M, van der Veldt, Astrid A M, Vreugdenhil, Gerard, Westgeest, Hans M, Wouters, Michel W J M, van Akkooi, Alexander C J, Pathologie Pathologen staf, Cancer, MS Medische Oncologie, Infection & Immunity, Blankenstein, Stephanie A, Bonenkamp, Johannes J, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, Blank, Christian U, Blokx, Willeke A M, Boers-Sonderen, Marye J, van den Eertwegh, Alfons J M, Franken, Margreet G, de Groot, Jan Willem B, Haanen, John B A G, Hospers, Geke A P, Kapiteijn, Ellen W, van Not, Olivier J, Piersma, Djura, van Rijn, Rozemarijn S, Suijkerbuijk, Karijn P M, van der Veldt, Astrid A M, Vreugdenhil, Gerard, Westgeest, Hans M, Wouters, Michel W J M, and van Akkooi, Alexander C J

Published
2023

18. Tumor-Infiltrating Lymphocyte Therapy or Ipilimumab in Advanced Melanoma

Author

Rohaan, Maartje W, Borch, Troels H, van den Berg, Joost H, Met, Özcan, Kessels, Rob, Geukes Foppen, Marnix H, Stoltenborg Granhøj, Joachim, Nuijen, Bastiaan, Nijenhuis, Cynthia, Jedema, Inge, van Zon, Maaike, Scheij, Saskia, Beijnen, Jos H, Hansen, Marten, Voermans, Carlijn, Noringriis, Inge M, Monberg, Tine J, Holmstroem, Rikke B, Wever, Lidwina D V, van Dijk, Marloes, Grijpink-Ongering, Lindsay G, Valkenet, Ludy H M, Torres Acosta, Alejandro, Karger, Matthias, Borgers, Jessica S W, Ten Ham, Renske M T, Retèl, Valesca P, van Harten, Wim H, Lalezari, Ferry, van Tinteren, Harm, van der Veldt, Astrid A M, Hospers, Geke A P, Stevense-den Boer, Marion A M, Suijkerbuijk, Karijn P M, Aarts, Maureen J B, Piersma, Djura, van den Eertwegh, Alfons J M, de Groot, Jan-Willem B, Vreugdenhil, Gerard, Kapiteijn, Ellen, Boers-Sonderen, Marye J, Fiets, W Edward, van den Berkmortel, Franchette W P J, Ellebaek, Eva, Hölmich, Lisbet R, van Akkooi, Alexander C J, van Houdt, Winan J, Wouters, Michel W J M, van Thienen, Johannes V, Blank, Christian U, Meerveld-Eggink, Aafke, Klobuch, Sebastian, Wilgenhof, Sofie, Schumacher, Ton N, Donia, Marco, Svane, Inge Marie, Haanen, John B A G, Rohaan, Maartje W, Borch, Troels H, van den Berg, Joost H, Met, Özcan, Kessels, Rob, Geukes Foppen, Marnix H, Stoltenborg Granhøj, Joachim, Nuijen, Bastiaan, Nijenhuis, Cynthia, Jedema, Inge, van Zon, Maaike, Scheij, Saskia, Beijnen, Jos H, Hansen, Marten, Voermans, Carlijn, Noringriis, Inge M, Monberg, Tine J, Holmstroem, Rikke B, Wever, Lidwina D V, van Dijk, Marloes, Grijpink-Ongering, Lindsay G, Valkenet, Ludy H M, Torres Acosta, Alejandro, Karger, Matthias, Borgers, Jessica S W, Ten Ham, Renske M T, Retèl, Valesca P, van Harten, Wim H, Lalezari, Ferry, van Tinteren, Harm, van der Veldt, Astrid A M, Hospers, Geke A P, Stevense-den Boer, Marion A M, Suijkerbuijk, Karijn P M, Aarts, Maureen J B, Piersma, Djura, van den Eertwegh, Alfons J M, de Groot, Jan-Willem B, Vreugdenhil, Gerard, Kapiteijn, Ellen, Boers-Sonderen, Marye J, Fiets, W Edward, van den Berkmortel, Franchette W P J, Ellebaek, Eva, Hölmich, Lisbet R, van Akkooi, Alexander C J, van Houdt, Winan J, Wouters, Michel W J M, van Thienen, Johannes V, Blank, Christian U, Meerveld-Eggink, Aafke, Klobuch, Sebastian, Wilgenhof, Sofie, Schumacher, Ton N, Donia, Marco, Svane, Inge Marie, and Haanen, John B A G

Abstract

Background Immune checkpoint inhibitors and targeted therapies have dramatically improved outcomes in patients with advanced melanoma, but approximately half these patients will not have a durable benefit. Phase 1-2 trials of adoptive cell therapy with tumor-infiltrating lymphocytes (TILs) have shown promising responses, but data from phase 3 trials are lacking to determine the role of TILs in treating advanced melanoma. Methods In this phase 3, multicenter, open-label trial, we randomly assigned patients with unresectable stage IIIC or IV melanoma in a 1:1 ratio to receive TIL or anti-cytotoxic T-lymphocyte antigen 4 therapy (ipilimumab at 3 mg per kilogram of body weight). Infusion of at least 5×109 TILs was preceded by nonmyeloablative, lymphodepleting chemotherapy (cyclophosphamide plus fludarabine) and followed by high-dose interleukin-2. The primary end point was progression-free survival. Results A total of 168 patients (86% with disease refractory to anti-programmed death 1 treatment) were assigned to receive TILs (84 patients) or ipilimumab (84 patients). In the intention-to-treat population, median progression-free survival was 7.2 months (95% confidence interval [CI], 4.2 to 13.1) in the TIL group and 3.1 months (95% CI, 3.0 to 4.3) in the ipilimumab group (hazard ratio for progression or death, 0.50; 95% CI, 0.35 to 0.72; P<0.001); 49% (95% CI, 38 to 60) and 21% (95% CI, 13 to 32) of the patients, respectively, had an objective response. Median overall survival was 25.8 months (95% CI, 18.2 to not reached) in the TIL group and 18.9 months (95% CI, 13.8 to 32.6) in the ipilimumab group. Treatment-related adverse events of grade 3 or higher occurred in all patients who received TILs and in 57% of those who received ipilimumab; in the TIL group, these events were mainly chemotherapy-related myelosuppression. Conclusions In patients with advanced melanoma, progression-free survival was significantly longer among those who received TIL therapy than amon

Published
2022

19. Response to immune checkpoint inhibitors in acral melanoma:A nationwide cohort study

Author

van Not, Olivier J, de Meza, Melissa M, van den Eertwegh, Alfons J M, Haanen, John B, Blank, Christian U, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, van Breeschoten, Jesper, de Groot, Jan-Willem B, Hospers, Geke A P, Ismail, Rawa K, Kapiteijn, Ellen, Piersma, Djura, van Rijn, Roos S, Stevense-den Boer, Marion A M, van der Veldt, Astrid A M, Vreugdenhil, Gerard, Bonenkamp, Han J, Boers-Sonderen, Marye J, Blokx, Willeke A M, Wouters, Michel W J M, Suijkerbuijk, Karijn P M, van Not, Olivier J, de Meza, Melissa M, van den Eertwegh, Alfons J M, Haanen, John B, Blank, Christian U, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, van Breeschoten, Jesper, de Groot, Jan-Willem B, Hospers, Geke A P, Ismail, Rawa K, Kapiteijn, Ellen, Piersma, Djura, van Rijn, Roos S, Stevense-den Boer, Marion A M, van der Veldt, Astrid A M, Vreugdenhil, Gerard, Bonenkamp, Han J, Boers-Sonderen, Marye J, Blokx, Willeke A M, Wouters, Michel W J M, and Suijkerbuijk, Karijn P M

Abstract

Background: Recent reports suggest the limited efficacy of immune checkpoints inhibitors in advanced acral melanoma (AM). This study aims to investigate the clinical outcomes of immune checkpoint inhibitors in patients with stage III and IV AM and compare them to cutaneous melanoma (CM). Methods: We included patients with advanced AM and CM treated with first-line anti-programmed cell death (PD)-1 monotherapy or ipilimumab-nivolumab registered in the prospective nationwide Dutch Melanoma Treatment Registry. Objective response rates, progression-free survival (PFS) and overall survival (OS) were calculated. A Cox proportional hazard model was used to assess the prognostic factors with PFS and OS. Results: In total, 2058 patients (88 AM and 1970 CM) with advanced melanoma were included. First-line objective response rates were 34% for AM versus 54% for CM in the advanced anti-PD-1 cohort and 33% for AM versus 53% for CM in the advanced ipilimumab-nivolumab cohort. The Median PFS was significantly shorter for anti-PD-1 treated AM patients (3.1 months; 95%CI: 2.8–5.6) than patients with CM (10.1 months; 95%CI: 8.5–12.2) (P < 0.001). In patients with advanced melanoma, AM was significantly associated with a higher risk of progression (HRadj 1.63; 95%CI: 1.26–2.11; P < 0.001) and death (HRadj 1.54; 95%CI: 1.15–2.06; P = 0.004) than CM. Conclusions: This study shows lower effectiveness of anti-PD -1 monotherapy and ipilimumab-nivolumab in AM, with lower response rates, PFS and OS than CM. This group of patients should be prioritised in the development of alternative treatment strategies.

Published
2022

20. End-of-Life Use of Systemic Therapy in Patients With Advanced Melanoma: A Nationwide Cohort Study

Author

van Breeschoten, Jesper, Ismail, Rawa K, Wouters, Michel W J M, Hilarius, Doranne L, de Wreede, Liesbeth C, Haanen, John B, Blank, Christian U, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, de Groot, Jan Willem B, Hospers, Geke A P, Kapiteijn, Ellen, Piersma, Djura, van Rijn, Rozemarijn S, Stevense-den Boer, Marion A, van der Veldt, Astrid A M, Vreugdenhil, Gerard, Boers-Sonderen, Marye J, Suijkerbuijk, Karijn P M, van den Eertwegh, Alfons J M, van Breeschoten, Jesper, Ismail, Rawa K, Wouters, Michel W J M, Hilarius, Doranne L, de Wreede, Liesbeth C, Haanen, John B, Blank, Christian U, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, de Groot, Jan Willem B, Hospers, Geke A P, Kapiteijn, Ellen, Piersma, Djura, van Rijn, Rozemarijn S, Stevense-den Boer, Marion A, van der Veldt, Astrid A M, Vreugdenhil, Gerard, Boers-Sonderen, Marye J, Suijkerbuijk, Karijn P M, and van den Eertwegh, Alfons J M

Abstract

PURPOSE: The introduction of immune checkpoint inhibitors and targeted therapies improved the overall survival of patients with advanced melanoma. It is not known how often these costly treatments with potential serious side effects are ineffectively applied in the last phase of life. This study aimed to investigate the start of a new systemic therapy within 45 and 90 days of death in Dutch patients with advanced melanoma.METHODS: We selected patients who were diagnosed with unresectable IIIC or stage IV melanoma, registered in the Dutch Melanoma Treatment Registry, and died between 2013 and 2019. Primary outcome was the probability of starting a new systemic therapy 45 and 90 days before death. Secondary outcomes were type of systemic therapy started, grade 3/4 adverse events (AEs), and the total costs of systemic therapies.RESULTS: Between 2013 and 2019, 3,797 patients with unresectable IIIC or stage IV melanoma were entered in the registry and died. The percentage of patients receiving a new systemic therapy within 45 and 90 days before death was significantly different between Dutch melanoma centers (varying from 6% to 23% and 20% to 46%, respectively). Thirteen percent of patients (n = 146) developed grade 3/4 AEs in the last period before death. The majority of patients with an AE required hospital admission (n = 102, 69.6%). Mean total costs of systemic therapy per cohort year of the patients who received a new systemic therapy within 90 days before death were 2.3%-2.8% of the total costs spent on melanoma therapies.CONCLUSION: The minority of Dutch patients with metastatic melanoma started a new systemic therapy in the last phase of life. However, the percentages varied between Dutch melanoma centers. Financial impact of these therapies in the last phase of life is relatively small.

Published
2022

21. Tumor-Infiltrating Lymphocyte Therapy or Ipilimumab in Advanced Melanoma

Author

HEE, MS Medische Oncologie, Cancer, Infection & Immunity, Rohaan, Maartje W, Borch, Troels H, van den Berg, Joost H, Met, Özcan, Kessels, Rob, Geukes Foppen, Marnix H, Stoltenborg Granhøj, Joachim, Nuijen, Bastiaan, Nijenhuis, Cynthia, Jedema, Inge, van Zon, Maaike, Scheij, Saskia, Beijnen, Jos H, Hansen, Marten, Voermans, Carlijn, Noringriis, Inge M, Monberg, Tine J, Holmstroem, Rikke B, Wever, Lidwina D V, van Dijk, Marloes, Grijpink-Ongering, Lindsay G, Valkenet, Ludy H M, Torres Acosta, Alejandro, Karger, Matthias, Borgers, Jessica S W, Ten Ham, Renske M T, Retèl, Valesca P, van Harten, Wim H, Lalezari, Ferry, van Tinteren, Harm, van der Veldt, Astrid A M, Hospers, Geke A P, Stevense-den Boer, Marion A M, Suijkerbuijk, Karijn P M, Aarts, Maureen J B, Piersma, Djura, van den Eertwegh, Alfons J M, de Groot, Jan-Willem B, Vreugdenhil, Gerard, Kapiteijn, Ellen, Boers-Sonderen, Marye J, Fiets, W Edward, van den Berkmortel, Franchette W P J, Ellebaek, Eva, Hölmich, Lisbet R, van Akkooi, Alexander C J, van Houdt, Winan J, Wouters, Michel W J M, van Thienen, Johannes V, Blank, Christian U, Meerveld-Eggink, Aafke, Klobuch, Sebastian, Wilgenhof, Sofie, Schumacher, Ton N, Donia, Marco, Svane, Inge Marie, Haanen, John B A G, HEE, MS Medische Oncologie, Cancer, Infection & Immunity, Rohaan, Maartje W, Borch, Troels H, van den Berg, Joost H, Met, Özcan, Kessels, Rob, Geukes Foppen, Marnix H, Stoltenborg Granhøj, Joachim, Nuijen, Bastiaan, Nijenhuis, Cynthia, Jedema, Inge, van Zon, Maaike, Scheij, Saskia, Beijnen, Jos H, Hansen, Marten, Voermans, Carlijn, Noringriis, Inge M, Monberg, Tine J, Holmstroem, Rikke B, Wever, Lidwina D V, van Dijk, Marloes, Grijpink-Ongering, Lindsay G, Valkenet, Ludy H M, Torres Acosta, Alejandro, Karger, Matthias, Borgers, Jessica S W, Ten Ham, Renske M T, Retèl, Valesca P, van Harten, Wim H, Lalezari, Ferry, van Tinteren, Harm, van der Veldt, Astrid A M, Hospers, Geke A P, Stevense-den Boer, Marion A M, Suijkerbuijk, Karijn P M, Aarts, Maureen J B, Piersma, Djura, van den Eertwegh, Alfons J M, de Groot, Jan-Willem B, Vreugdenhil, Gerard, Kapiteijn, Ellen, Boers-Sonderen, Marye J, Fiets, W Edward, van den Berkmortel, Franchette W P J, Ellebaek, Eva, Hölmich, Lisbet R, van Akkooi, Alexander C J, van Houdt, Winan J, Wouters, Michel W J M, van Thienen, Johannes V, Blank, Christian U, Meerveld-Eggink, Aafke, Klobuch, Sebastian, Wilgenhof, Sofie, Schumacher, Ton N, Donia, Marco, Svane, Inge Marie, and Haanen, John B A G

Published
2022

22. BRAF and NRAS Mutation Status and Response to Checkpoint Inhibition in Advanced Melanoma

Author

Cancer, MS Medische Oncologie, Pathologie Pathologen staf, Pathologie Moleculair, Infection & Immunity, van Not, Olivier J, Blokx, Willeke A M, van den Eertwegh, Alfons J M, de Meza, Melissa M, Haanen, John B, Blank, Christian U, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, de Groot, Jan Willem B, Hospers, Geke A P, Kapiteijn, Ellen, Piersma, Djura, van Rijn, Rozemarijn S, Stevense-den Boer, Marion, van der Veldt, Astrid A M, Boers-Sonderen, Marye J, Jansen, Anne M L, Wouters, Michel W J M, Suijkerbuijk, Karijn P M, Cancer, MS Medische Oncologie, Pathologie Pathologen staf, Pathologie Moleculair, Infection & Immunity, van Not, Olivier J, Blokx, Willeke A M, van den Eertwegh, Alfons J M, de Meza, Melissa M, Haanen, John B, Blank, Christian U, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, de Groot, Jan Willem B, Hospers, Geke A P, Kapiteijn, Ellen, Piersma, Djura, van Rijn, Rozemarijn S, Stevense-den Boer, Marion, van der Veldt, Astrid A M, Boers-Sonderen, Marye J, Jansen, Anne M L, Wouters, Michel W J M, and Suijkerbuijk, Karijn P M

Published
2022

23. Response to immune checkpoint inhibitors in acral melanoma: A nationwide cohort study

Author

Pathologie Pathologen staf, Cancer, MS Medische Oncologie, Infection & Immunity, van Not, Olivier J, de Meza, Melissa M, van den Eertwegh, Alfons J M, Haanen, John B, Blank, Christian U, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, van Breeschoten, Jesper, de Groot, Jan-Willem B, Hospers, Geke A P, Ismail, Rawa K, Kapiteijn, Ellen, Piersma, Djura, van Rijn, Roos S, Stevense-den Boer, Marion A M, van der Veldt, Astrid A M, Vreugdenhil, Gerard, Bonenkamp, Han J, Boers-Sonderen, Marye J, Blokx, Willeke A M, Wouters, Michel W J M, Suijkerbuijk, Karijn P M, Pathologie Pathologen staf, Cancer, MS Medische Oncologie, Infection & Immunity, van Not, Olivier J, de Meza, Melissa M, van den Eertwegh, Alfons J M, Haanen, John B, Blank, Christian U, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, van Breeschoten, Jesper, de Groot, Jan-Willem B, Hospers, Geke A P, Ismail, Rawa K, Kapiteijn, Ellen, Piersma, Djura, van Rijn, Roos S, Stevense-den Boer, Marion A M, van der Veldt, Astrid A M, Vreugdenhil, Gerard, Bonenkamp, Han J, Boers-Sonderen, Marye J, Blokx, Willeke A M, Wouters, Michel W J M, and Suijkerbuijk, Karijn P M

Published
2022

24. Discontinuation of anti-PD-1 monotherapy in advanced melanoma - outcomes of daily clinical practice

Author

MS Medische Oncologie, Infection & Immunity, Cancer, van Zeijl, Michiel C T, van den Eertwegh, Alfons J M, Wouters, Michel W J M, de Wreede, Liesbeth C, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, de Groot, Jan-Willem B, Hospers, Geke A P, Kapiteijn, Ellen, Piersma, Djura, van Rijn, Rozemarijn S, Suijkerbuijk, Karijn P M, Ten Tije, Albert J, van der Veldt, Astrid A M, Vreugdenhil, Gerard, van der Hoeven, Jacobus J M, Haanen, John B A G, MS Medische Oncologie, Infection & Immunity, Cancer, van Zeijl, Michiel C T, van den Eertwegh, Alfons J M, Wouters, Michel W J M, de Wreede, Liesbeth C, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, de Groot, Jan-Willem B, Hospers, Geke A P, Kapiteijn, Ellen, Piersma, Djura, van Rijn, Rozemarijn S, Suijkerbuijk, Karijn P M, Ten Tije, Albert J, van der Veldt, Astrid A M, Vreugdenhil, Gerard, van der Hoeven, Jacobus J M, and Haanen, John B A G

Published
2022

26. Long-Term Survival in Patients With Advanced Melanoma.

Author

van Not, Olivier J., van den Eertwegh, Alfons J. M., Jalving, Hilde, Bloem, Manja, Haanen, John B., van Rijn, Rozemarijn S., Aarts, Maureen J. B., van den Berkmortel, Franchette W. P. J., Blank, Christian U., Boers-Sonderen, Marye J., de Groot J. W. B., Jan Willem, Hospers, Geke A. P., Kapiteijn, Ellen, Leeneman, Brenda, D., Piersma, Stevense-den Boer, Marion, van der Veldt, Astrid A. M., Vreugdenhil G., Gerard, Wouters, Michel W. J. M., and Blokx, Willeke A. M.

Published
2024
Full Text
View/download PDF

27. T cell profiling reveals high CD4+CTLA-4+ T cell frequency as dominant predictor for survival after Prostate GVAX/ipilimumab treatment

Author

Santegoets, Saskia J. A. M., Stam, Anita G. M., Lougheed, Sinéad M., Gall, Helen, Scholten, Petra E. T., Reijm, Martine, Jooss, Karin, Sacks, Natalie, Hege, Kristen, Lowy, Israel, Cuillerot, Jean-Marie, von Blomberg, B. Mary E., Scheper, Rik J., van den Eertwegh, Alfons J. M., Gerritsen, Winald R., and de Gruijl, Tanja D.

Published
2013
Full Text
View/download PDF

28. CD169 Defines Activated CD14+ Monocytes With Enhanced CD8+ T Cell Activation Capacity

Author

Affandi, Alsya J., primary, Olesek, Katarzyna, additional, Grabowska, Joanna, additional, Nijen Twilhaar, Maarten K., additional, Rodríguez, Ernesto, additional, Saris, Anno, additional, Zwart, Eline S., additional, Nossent, Esther J., additional, Kalay, Hakan, additional, de Kok, Michael, additional, Kazemier, Geert, additional, Stöckl, Johannes, additional, van den Eertwegh, Alfons J. M., additional, de Gruijl, Tanja D., additional, Garcia-Vallejo, Juan J., additional, Storm, Gert, additional, van Kooyk, Yvette, additional, and den Haan, Joke M. M., additional

Published
2021
Full Text
View/download PDF

29. CD169 Defines Activated CD14+ Monocytes With Enhanced CD8+ T Cell Activation Capacity

Author

Afd Pharmaceutics, Pharmaceutics, Affandi, Alsya J, Olesek, Katarzyna, Grabowska, Joanna, Nijen Twilhaar, Maarten K, Rodríguez, Ernesto, Saris, Anno, Zwart, Eline S, Nossent, Esther J, Kalay, Hakan, de Kok, Michael, Kazemier, Geert, Stöckl, Johannes, van den Eertwegh, Alfons J M, de Gruijl, Tanja D, Garcia-Vallejo, Juan J, Storm, Gert, van Kooyk, Yvette, den Haan, Joke M M, Afd Pharmaceutics, Pharmaceutics, Affandi, Alsya J, Olesek, Katarzyna, Grabowska, Joanna, Nijen Twilhaar, Maarten K, Rodríguez, Ernesto, Saris, Anno, Zwart, Eline S, Nossent, Esther J, Kalay, Hakan, de Kok, Michael, Kazemier, Geert, Stöckl, Johannes, van den Eertwegh, Alfons J M, de Gruijl, Tanja D, Garcia-Vallejo, Juan J, Storm, Gert, van Kooyk, Yvette, and den Haan, Joke M M

Published
2021

30. Nationwide Outcomes of Advanced Melanoma According to BRAFV600 Status

Author

MS Medische Oncologie, Infection & Immunity, Cancer, Pathologie Pathologen staf, van Breeschoten, Jesper, Wouters, Michel W J M, de Wreede, Liesbeth C, Hilarius, Doranne H, Haanen, John B, Blank, Christian U, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, de Groot, Jan-Willem B, Hospers, Geke A P, Kapiteijn, Ellen, Piersma, Djura, van Rijn, Rozemarijn S, Suijkerbuijk, Karijn P M, Blokx, Willeke A M, Ten Tije, Albert J, van der Veldt, Astrid A M, Vreugdenhil, Gerard, Boers, Marye J, van den Eertwegh, Alfons J M, MS Medische Oncologie, Infection & Immunity, Cancer, Pathologie Pathologen staf, van Breeschoten, Jesper, Wouters, Michel W J M, de Wreede, Liesbeth C, Hilarius, Doranne H, Haanen, John B, Blank, Christian U, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, de Groot, Jan-Willem B, Hospers, Geke A P, Kapiteijn, Ellen, Piersma, Djura, van Rijn, Rozemarijn S, Suijkerbuijk, Karijn P M, Blokx, Willeke A M, Ten Tije, Albert J, van der Veldt, Astrid A M, Vreugdenhil, Gerard, Boers, Marye J, and van den Eertwegh, Alfons J M

Published
2021

33. Surgery for Unresectable Stage IIIC and IV Melanoma in the Era of New Systemic Therapy

Author

Blankenstein, Stephanie A, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, Boers-Sonderen, Marye J, van den Eertwegh, Alfons J M, Franken, Margreet G, de Groot, Jan Willem B, Haanen, John B A G, Hospers, Geke A P, Kapiteijn, Ellen, Piersma, Djura, van Rijn, Rozemarijn S, Suijkerbuijk, Karijn P M, Ten Tije, Albert J, van der Veldt, Astrid A M, Vreugdenhil, Gerard, Wouters, Michel W J M, van Akkooi, Alexander C J, Blankenstein, Stephanie A, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, Boers-Sonderen, Marye J, van den Eertwegh, Alfons J M, Franken, Margreet G, de Groot, Jan Willem B, Haanen, John B A G, Hospers, Geke A P, Kapiteijn, Ellen, Piersma, Djura, van Rijn, Rozemarijn S, Suijkerbuijk, Karijn P M, Ten Tije, Albert J, van der Veldt, Astrid A M, Vreugdenhil, Gerard, Wouters, Michel W J M, and van Akkooi, Alexander C J

Published
2020

34. Healthcare Costs of Metastatic Cutaneous Melanoma in the Era of Immunotherapeutic and Targeted Drugs

Author

Leeneman, Brenda, Uyl-de Groot, Carin A, Aarts, Maureen J B, van Akkooi, Alexander C J, van den Berkmortel, Franchette W P J, van den Eertwegh, Alfons J M, de Groot, Jan Willem B, Herbschleb, Karin H, van der Hoeven, Jacobus J M, Hospers, Geke A P, Kapiteijn, Ellen, Piersma, Djura, van Rijn, Rozemarijn S, Suijkerbuijk, Karijn P M, Ten Tije, Albert J, van der Veldt, Astrid A M, Vreugdenhil, Gerard, Wouters, Michel W J M, Haanen, John B A G, Franken, Margreet G, Leeneman, Brenda, Uyl-de Groot, Carin A, Aarts, Maureen J B, van Akkooi, Alexander C J, van den Berkmortel, Franchette W P J, van den Eertwegh, Alfons J M, de Groot, Jan Willem B, Herbschleb, Karin H, van der Hoeven, Jacobus J M, Hospers, Geke A P, Kapiteijn, Ellen, Piersma, Djura, van Rijn, Rozemarijn S, Suijkerbuijk, Karijn P M, Ten Tije, Albert J, van der Veldt, Astrid A M, Vreugdenhil, Gerard, Wouters, Michel W J M, Haanen, John B A G, and Franken, Margreet G

Published
2020

35. Selective tumor antigen vaccine delivery to human CD169+ antigen-presenting cells using ganglioside-liposomes

Author

Afd Pharmaceutics, Pharmaceutics, Affandi, Alsya J, Grabowska, Joanna, Olesek, Katarzyna, Lopez Venegas, Miguel, Barbaria, Arnaud, Rodríguez, Ernesto, Mulder, Patrick P G, Pijffers, Helen J, Ambrosini, Martino, Kalay, Hakan, O'Toole, Tom, Zwart, Eline S, Kazemier, Geert, Nazmi, Kamran, Bikker, Floris J, Stöckl, Johannes, van den Eertwegh, Alfons J M, de Gruijl, Tanja D, Storm, Gert, van Kooyk, Yvette, den Haan, Joke M M, Afd Pharmaceutics, Pharmaceutics, Affandi, Alsya J, Grabowska, Joanna, Olesek, Katarzyna, Lopez Venegas, Miguel, Barbaria, Arnaud, Rodríguez, Ernesto, Mulder, Patrick P G, Pijffers, Helen J, Ambrosini, Martino, Kalay, Hakan, O'Toole, Tom, Zwart, Eline S, Kazemier, Geert, Nazmi, Kamran, Bikker, Floris J, Stöckl, Johannes, van den Eertwegh, Alfons J M, de Gruijl, Tanja D, Storm, Gert, van Kooyk, Yvette, and den Haan, Joke M M

Published
2020

36. Surgery for Unresectable Stage IIIC and IV Melanoma in the Era of New Systemic Therapy

Author

MS Medische Oncologie, Infection & Immunity, Cancer, Blankenstein, Stephanie A, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, Boers-Sonderen, Marye J, van den Eertwegh, Alfons J M, Franken, Margreet G, de Groot, Jan Willem B, Haanen, John B A G, Hospers, Geke A P, Kapiteijn, Ellen, Piersma, Djura, van Rijn, Rozemarijn S, Suijkerbuijk, Karijn P M, Ten Tije, Albert J, van der Veldt, Astrid A M, Vreugdenhil, Gerard, Wouters, Michel W J M, van Akkooi, Alexander C J, MS Medische Oncologie, Infection & Immunity, Cancer, Blankenstein, Stephanie A, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, Boers-Sonderen, Marye J, van den Eertwegh, Alfons J M, Franken, Margreet G, de Groot, Jan Willem B, Haanen, John B A G, Hospers, Geke A P, Kapiteijn, Ellen, Piersma, Djura, van Rijn, Rozemarijn S, Suijkerbuijk, Karijn P M, Ten Tije, Albert J, van der Veldt, Astrid A M, Vreugdenhil, Gerard, Wouters, Michel W J M, and van Akkooi, Alexander C J

Published
2020

37. Healthcare Costs of Metastatic Cutaneous Melanoma in the Era of Immunotherapeutic and Targeted Drugs

Author

MS Medische Oncologie, Infection & Immunity, Cancer, Leeneman, Brenda, Uyl-de Groot, Carin A, Aarts, Maureen J B, van Akkooi, Alexander C J, van den Berkmortel, Franchette W P J, van den Eertwegh, Alfons J M, de Groot, Jan Willem B, Herbschleb, Karin H, van der Hoeven, Jacobus J M, Hospers, Geke A P, Kapiteijn, Ellen, Piersma, Djura, van Rijn, Rozemarijn S, Suijkerbuijk, Karijn P M, Ten Tije, Albert J, van der Veldt, Astrid A M, Vreugdenhil, Gerard, Wouters, Michel W J M, Haanen, John B A G, Franken, Margreet G, MS Medische Oncologie, Infection & Immunity, Cancer, Leeneman, Brenda, Uyl-de Groot, Carin A, Aarts, Maureen J B, van Akkooi, Alexander C J, van den Berkmortel, Franchette W P J, van den Eertwegh, Alfons J M, de Groot, Jan Willem B, Herbschleb, Karin H, van der Hoeven, Jacobus J M, Hospers, Geke A P, Kapiteijn, Ellen, Piersma, Djura, van Rijn, Rozemarijn S, Suijkerbuijk, Karijn P M, Ten Tije, Albert J, van der Veldt, Astrid A M, Vreugdenhil, Gerard, Wouters, Michel W J M, Haanen, John B A G, and Franken, Margreet G

Published
2020

38. Real-world Outcomes of First-line Anti-PD-1 Therapy for Advanced Melanoma: A Nationwide Population-based Study

Author

MS Medische Oncologie, Infection & Immunity, Cancer, van Zeijl, Michiel C T, Haanen, John B A G, Wouters, Michel W J M, de Wreede, Liesbeth C, Jochems, Anouk, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, de Groot, Jan Willem B, Hospers, Geke A P, Kapiteijn, Ellen W, Piersma, Djura, van Rijn, Rozemarijn S, Suijkerbuijk, Karijn P M, Ten Tije, Albert J, van der Veldt, Astrid A M, Vreugdenhil, Gerard, van der Hoeven, Koos J M, van den Eertwegh, Alfons J M, MS Medische Oncologie, Infection & Immunity, Cancer, van Zeijl, Michiel C T, Haanen, John B A G, Wouters, Michel W J M, de Wreede, Liesbeth C, Jochems, Anouk, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, de Groot, Jan Willem B, Hospers, Geke A P, Kapiteijn, Ellen W, Piersma, Djura, van Rijn, Rozemarijn S, Suijkerbuijk, Karijn P M, Ten Tije, Albert J, van der Veldt, Astrid A M, Vreugdenhil, Gerard, van der Hoeven, Koos J M, and van den Eertwegh, Alfons J M

Published
2020

39. Selective tumor antigen vaccine delivery to human CD169 + antigen-presenting cells using ganglioside-liposomes

Author

Affandi, Alsya J., primary, Grabowska, Joanna, additional, Olesek, Katarzyna, additional, Lopez Venegas, Miguel, additional, Barbaria, Arnaud, additional, Rodríguez, Ernesto, additional, Mulder, Patrick P. G., additional, Pijffers, Helen J., additional, Ambrosini, Martino, additional, Kalay, Hakan, additional, O’Toole, Tom, additional, Zwart, Eline S., additional, Kazemier, Geert, additional, Nazmi, Kamran, additional, Bikker, Floris J., additional, Stöckl, Johannes, additional, van den Eertwegh, Alfons J. M., additional, de Gruijl, Tanja D., additional, Storm, Gert, additional, van Kooyk, Yvette, additional, and den Haan, Joke M. M., additional

Published
2020
Full Text
View/download PDF

40. Surgery for Unresectable Stage IIIC and IV Melanoma in the Era of New Systemic Therapy

Author

Blankenstein, Stephanie A., primary, Aarts, Maureen J. B., additional, van den Berkmortel, Franchette W. P. J., additional, Boers-Sonderen, Marye J., additional, van den Eertwegh, Alfons J. M., additional, Franken, Margreet G., additional, de Groot, Jan Willem B., additional, Haanen, John B. A. G., additional, Hospers, Geke A. P., additional, Kapiteijn, Ellen, additional, Piersma, Djura, additional, van Rijn, Rozemarijn S., additional, Suijkerbuijk, Karijn P. M., additional, ten Tije, Albert J., additional, van der Veldt, Astrid A. M., additional, Vreugdenhil, Gerard, additional, Wouters, Michel W. J. M., additional, and van Akkooi, Alexander C. J., additional

Published
2020
Full Text
View/download PDF

41. Healthcare Costs of Metastatic Cutaneous Melanoma in the Era of Immunotherapeutic and Targeted Drugs

Author

Leeneman, Brenda, primary, Uyl-de Groot, Carin A., additional, Aarts, Maureen J. B., additional, van Akkooi, Alexander C. J., additional, van den Berkmortel, Franchette W. P. J., additional, van den Eertwegh, Alfons J. M., additional, de Groot, Jan Willem B., additional, Herbschleb, Karin H., additional, van der Hoeven, Jacobus J. M., additional, Hospers, Geke A. P., additional, Kapiteijn, Ellen, additional, Piersma, Djura, additional, van Rijn, Rozemarijn S., additional, Suijkerbuijk, Karijn P. M., additional, ten Tije, Albert J., additional, van der Veldt, Astrid A. M., additional, Vreugdenhil, Gerard, additional, Wouters, Michel W. J. M., additional, Haanen, John B. A. G., additional, and Franken, Margreet G., additional

Published
2020
Full Text
View/download PDF

42. In the mix: the potential benefits of adding GM-CSF to CpG-B in the local treatment of patients with early-stage melanoma

Author

Koster, Bas D., primary, de Jong, Tamarah D., additional, van den Hout, Mari F. C. M., additional, Sluijter, Berbel J. R., additional, Vuylsteke, Ronald J. C. L. M., additional, Molenkamp, Barbara G., additional, Vosslamber, Saskia, additional, van den Tol, M. Petrousjka, additional, van den Eertwegh, Alfons J. M., additional, and de Gruijl, Tanja D., additional

Published
2019
Full Text
View/download PDF

43. Correction to: Autologous tumor cell vaccination combined with systemic CpG-B and IFN-α promotes immune activation and induces clinical responses in patients with metastatic renal cell carcinoma: a phase II trial (Cancer Immunology, Immunotherapy, (2019), 10.1007/s00262-019-02320-0)

Author

Koster, Bas D., Santegoets, Saskia J. A. M., Harting, Jorien, Baars, Arnold, van Ham, S. Marieke, Scheper, Rik J., Hooijberg, Erik, de Gruijl, Tanja D., and van den Eertwegh, Alfons J. M.

Abstract

In the original publication of the article the following abstract and keywords were inadvertently omitted. Abstract Background In this study the toxicity and efficacy of an irradiated autologous tumor cell vaccine (ATV) co-injected with a class-B CpG oligodeoxynucleotide (CpG-B) and GMCSF, followed by systemic CpG-B and IFN-α administration, were examined in patients with metastatic renal cell carcinoma (mRCC). Methods A single-arm Phase II trial was conducted, in which patients with mRCC were intradermally injected with a minimum of three whole-cell vaccines containing 0.7–1.3 × 107 irradiated autologous tumor cells (ATC), admixed with 1 mg CpG-B and 100 μg GM-CSF, followed by bi-weekly s.c. injections with 8 mg CpG-B and s.c. injections with 6 MU IFN-α three times per week. Results Fifteen patients were treated according to the protocol. Treatment was well tolerated. Objective clinical responses occurred in three patients, including one longterm complete response. Disease stabilization occurred in another three patients. Positive delayed type hypersensitivity (DTH) responses to ATC were absent before treatment but present in 13 out of 15 patients during treatment. Immune monitoring revealed activation of plasmacytoid dendritic cells, non-classical monocytes and up-regulation of both PD-1 and CTLA4 on effector T cells upon treatment. Moreover, a pre-existing ex vivo IFN-γ response to ATC was associated with clinical response. Conclusions ATV combined with systemic CpG-B and IFN-α is tolerable, safe, immunogenic and able to elicit antitumor responses in patients with mRCC. Immune activation and treatment-induced up-regulation of PD-1 and CTLA4 on circulating T cells further suggest an added benefit of combining this approach with immune checkpoint blockade. Keywords Autologous tumor cell vaccination · CpG-B · IFN-alpha · GM-CSF · Metastatic renal cell cancer.

Published
2019

44. Switching to Immune Checkpoint Inhibitors upon Response to Targeted Therapy; The Road to Long-Term Survival in Advanced Melanoma Patients with Highly Elevated Serum LDH?

Author

Schouwenburg, Maartje G, Suijkerbuijk, Karijn P M, Koornstra, Rutger H T, Jochems, Anouk, van Zeijl, Michiel C T, van den Eertwegh, Alfons J M, Haanen, John B A G, Aarts, Maureen Jb, Akkooi, Alexander C J van, Berkmortel, Franchette W P J van den, Groot, Jan Willem B de, Hospers, Geke A P, Kapiteijn, Ellen, Kruit, Wim H, Piersma, Djura, van Rijn, Rozemarijn S, Ten Tije, Albert J, Vreugdenhil, Gerard, Hoeven, Jacobus J M van der, Wouters, Michel W J M, Schouwenburg, Maartje G, Suijkerbuijk, Karijn P M, Koornstra, Rutger H T, Jochems, Anouk, van Zeijl, Michiel C T, van den Eertwegh, Alfons J M, Haanen, John B A G, Aarts, Maureen Jb, Akkooi, Alexander C J van, Berkmortel, Franchette W P J van den, Groot, Jan Willem B de, Hospers, Geke A P, Kapiteijn, Ellen, Kruit, Wim H, Piersma, Djura, van Rijn, Rozemarijn S, Ten Tije, Albert J, Vreugdenhil, Gerard, Hoeven, Jacobus J M van der, and Wouters, Michel W J M

Published
2019

45. Switching to Immune Checkpoint Inhibitors upon Response to Targeted Therapy; The Road to Long-Term Survival in Advanced Melanoma Patients with Highly Elevated Serum LDH?

Author

MS Medische Oncologie, Cancer, Schouwenburg, Maartje G, Suijkerbuijk, Karijn P M, Koornstra, Rutger H T, Jochems, Anouk, van Zeijl, Michiel C T, van den Eertwegh, Alfons J M, Haanen, John B A G, Aarts, Maureen Jb, Akkooi, Alexander C J van, Berkmortel, Franchette W P J van den, Groot, Jan Willem B de, Hospers, Geke A P, Kapiteijn, Ellen, Kruit, Wim H, Piersma, Djura, van Rijn, Rozemarijn S, Ten Tije, Albert J, Vreugdenhil, Gerard, Hoeven, Jacobus J M van der, Wouters, Michel W J M, MS Medische Oncologie, Cancer, Schouwenburg, Maartje G, Suijkerbuijk, Karijn P M, Koornstra, Rutger H T, Jochems, Anouk, van Zeijl, Michiel C T, van den Eertwegh, Alfons J M, Haanen, John B A G, Aarts, Maureen Jb, Akkooi, Alexander C J van, Berkmortel, Franchette W P J van den, Groot, Jan Willem B de, Hospers, Geke A P, Kapiteijn, Ellen, Kruit, Wim H, Piersma, Djura, van Rijn, Rozemarijn S, Ten Tije, Albert J, Vreugdenhil, Gerard, Hoeven, Jacobus J M van der, and Wouters, Michel W J M

Published
2019

46. CD169 Defines Activated CD14+ Monocytes With Enhanced CD8+ T Cell Activation Capacity.

Author

Affandi, Alsya J., Olesek, Katarzyna, Grabowska, Joanna, Nijen Twilhaar, Maarten K., Rodríguez, Ernesto, Saris, Anno, Zwart, Eline S., Nossent, Esther J., Kalay, Hakan, de Kok, Michael, Kazemier, Geert, Stöckl, Johannes, van den Eertwegh, Alfons J. M., de Gruijl, Tanja D., Garcia-Vallejo, Juan J., Storm, Gert, van Kooyk, Yvette, and den Haan, Joke M. M.

Subjects
T cells, MONOCYTES, TYPE I interferons, COVID-19, ANTIGENS, HUMAN phenotype, T cell receptors
Abstract

Monocytes are antigen-presenting cells (APCs) that play diverse roles in promoting or regulating inflammatory responses, but their role in T cell stimulation is not well defined. In inflammatory conditions, monocytes frequently show increased expression of CD169/Siglec-1, a type-I interferon (IFN-I)-regulated protein. However, little is known about the phenotype and function of these CD169+ monocytes. Here, we have investigated the phenotype of human CD169+ monocytes in different diseases, their capacity to activate CD8+ T cells, and the potential for a targeted-vaccination approach. Using spectral flow cytometry, we detected CD169 expression by CD14+ CD16- classical and CD14+ CD16+ intermediate monocytes and unbiased analysis showed that they were distinct from dendritic cells, including the recently described CD14-expressing DC3. CD169+ monocytes expressed higher levels of co-stimulatory and HLA molecules, suggesting an increased activation state. IFNα treatment highly upregulated CD169 expression on CD14+ monocytes and boosted their capacity to cross-present antigen to CD8+ T cells. Furthermore, we observed CD169+ monocytes in virally-infected patients, including in the blood and bronchoalveolar lavage fluid of COVID-19 patients, as well as in the blood of patients with different types of cancers. Finally, we evaluated two CD169-targeting nanovaccine platforms, antibody-based and liposome-based, and we showed that CD169+ monocytes efficiently presented tumor-associated peptides gp100 and WT1 to antigen-specific CD8+ T cells. In conclusion, our data indicate that CD169+ monocytes are activated monocytes with enhanced CD8+ T cell stimulatory capacity and that they emerge as an interesting target in nanovaccine strategies, because of their presence in health and different diseases. [ABSTRACT FROM AUTHOR]

Published
2021
Full Text
View/download PDF

47. Selective tumor antigen vaccine delivery to human CD169+ antigen-presenting cells using ganglioside-liposomes.

Author

Affandi, Alsya J., Grabowska, Joanna, Olesek, Katarzyna, Venegas, Miguel Lopez, Barbaria, Arnaud, Ernesto Rodríguez, Mulder, Patrick P. G., Pijffers, Helen J., Ambrosini, Martino, Kalay, Hakan, O'Toole, Tom, Zwart, Eline S., Kazemier, Geert, Nazmi, Kamran, Bikker, Floris J., Stöckl, Johannes, van den Eertwegh, Alfons J. M., de Gruijl, Tanja D., Storm, Gert, and van Kooyk, Yvette

Subjects
TUMOR antigens, CANCER vaccines, ANTIGEN receptors, T cells, DENDRITIC cells
Abstract

Priming of CD8+ T cells by dendritic cells (DCs) is crucial for the generation of effective antitumor immune responses. Here, we describe a liposomal vaccine carrier that delivers tumor antigens to human CD169/Siglec-1+ antigen-presenting cells using gangliosides as targeting ligands. Ganglioside-liposomes specifically bound to CD169 and were internalized by in vitro-generated monocyte-derived DCs (moDCs) and macrophages and by ex vivo-isolated splenic macrophages in a CD169-dependent manner. In blood, high-dimensional reduction analysis revealed that ganglioside-liposomes specifically targeted CD14+ CD169+ monocytes and Axl+ CD169+ DCs. Liposomal codelivery of tumor antigen and Toll-like receptor ligand to CD169+ moDCs and Axl+ CD169+ DCs led to cytokine production and robust cross-presentation and activation of tumor antigen-specific CD8+ T cells. Finally, Axl+ CD169+ DCs were present in cancer patients and efficiently captured ganglioside-liposomes. Our findings demonstrate a nanovaccine platform targeting CD169+ DCs to drive antitumor T cell responses. [ABSTRACT FROM AUTHOR]

Published
2020
Full Text
View/download PDF

48. Vemurafenib plus cobimetinib in unresectable stage IIIc or stage IV melanoma

Author

van der Hiel, Bernies, Haanen, John B A G, Stokkel, Marcel P M, Peeper, Daniel S., Jimenez, Connie R., Beijnen, Jos H, van de Wiel, Bart A., Boellaard, Ronald, van den Eertwegh, Alfons J M, van Tinteren, H., Wessels, Lodewyk F A, Lolkema, Martijn P J K, Hoekstra, Otto S, Hospers, Geke A P, Brouwers, Adrienne H, Koornstra, R.H.T., Arens, A. I. J., de Vos, F. Y.F.L., Hobbelink, M. G.G., Kapiteijn, H. W., de Geus-Oei, L. F., Kruit, W. H.J., Verzijlbergen, F.J., Aarts, M. J.B., Mottaghy, F. M., de Groot, J. W.B., Knollema, S., Piersma, D., Agool, A., Vreugdenhil, Art, Liem, I H, van den Berkmortel, Franchette W P J, Schreurs, M.W., Guided Treatment in Optimal Selected Cancer Patients (GUTS), ​Basic and Translational Research and Imaging Methodology Development in Groningen (BRIDGE), AGEM - Re-generation and cancer of the digestive system, Medical oncology laboratory, CCA - Cancer Treatment and quality of life, and Medical oncology

Subjects
0301 basic medicine, Oncology, Pathology, Cancer Research, Indoles, Skin Neoplasms, medicine.medical_treatment, Resistance, Targeted therapy, BRAF-MUTATED MELANOMA, chemistry.chemical_compound, Study Protocol, 0302 clinical medicine, Piperidines, Antineoplastic Combined Chemotherapy Protocols, Medicine, METASTATIC MELANOMA, Multicenter Studies as Topic, Vemurafenib, Stage IIIc/IV melanoma, Melanoma, IN-VIVO, Sulfonamides, medicine.diagnostic_test, IMPROVED SURVIVAL, MEK inhibitor, RANDOMIZED CONTROLLED-TRIAL, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Treatment Outcome, Positron emission tomography, Research Design, 030220 oncology & carcinogenesis, medicine.drug, F-FLT, BRAF inhibitor, medicine.medical_specialty, PET/CT, CELL LUNG-CANCER, F-FDG, lcsh:RC254-282, Disease-Free Survival, F-18-FDG, 03 medical and health sciences, Clinical Trials, Phase II as Topic, Internal medicine, Genetics, Journal Article, Humans, Stage IIIC, F-18-FLT, MEK INHIBITION, LYMPH-NODE, Neoplasm Staging, Cobimetinib, PET-CT, business.industry, MUTATIONS, medicine.disease, MUTANT MELANOMA, 18F-FDG, 030104 developmental biology, chemistry, Drug Resistance, Neoplasm, Positron-Emission Tomography, 18F-FLT, Azetidines, business
Abstract

In patients with BRAFV600 mutated unresectable stage IIIc or metastatic melanoma, molecular targeted therapy with combined BRAF/MEK-inhibitor vemurafenib plus cobimetinib has shown a significantly improved progression-free survival and overall survival compared to treatment with vemurafenib alone. Nevertheless, the majority of BRAFV600 mutation-positive melanoma patients will eventually develop resistance to treatment. Molecular imaging with 18F-Fluorodeoxyglucose (18F-FDG) PET has been used to monitor response to vemurafenib in some BRAFV600 mutated metastatic melanoma patients, showing a rapid decline of 18F-FDG uptake within 2 weeks following treatment. Furthermore, preliminary results suggest that metabolic alterations might predict the development of resistance to treatment. 18F-Fluoro-3′-deoxy-3’L-fluorothymidine (18F-FLT), a PET-tracer visualizing proliferation, might be more suitable to predict response or resistance to therapy than 18F-FDG. This phase II, open-label, multicenter study evaluates whether metabolic response to treatment with vemurafenib plus cobimetinib in the first 7 weeks as assessed by 18F-FDG/18F-FLT PET can predict progression-free survival and whether early changes in 18F-FDG/18F-FLT can be used for early detection of treatment response compared to standard response assessment with RECISTv1.1 ceCT at 7 weeks. Ninety patients with BRAFV600E/K mutated unresectable stage IIIc/IV melanoma will be included. Prior to and during treatment all patients will undergo 18F-FDG PET/CT and in 25 patients additional 18F-FLT PET/CT is performed. Histopathological tumor characterization is assessed in a subset of 40 patients to unravel mechanisms of resistance. Furthermore, in all patients, blood samples are taken for pharmacokinetic analysis of vemurafenib/cobimetinib. Outcomes are correlated with PET/CT-imaging and therapy response. The results of this study will help in linking PET measured metabolic alterations induced by targeted therapy of BRAFV600 mutated melanoma to molecular changes within the tumor. We will be able to correlate both 18F-FDG and 18F-FLT PET to outcome and decide on the best modality to predict long-term remissions to combined BRAF/MEK-inhibitors. Results coming from this study may help in identifying responders from non-responders early after the initiation of therapy and reveal early development of resistance to vemurafenib/cobimetinib. Furthermore, we believe that the results can be fundamental for further optimizing individual patient treatment. Clinicaltrials.gov identifier: NCT02414750. Registered 10 April 2015, retrospectively registered.

Published
2017

49. Vemurafenib plus cobimetinib in unresectable stage IIIc or stage IV melanoma : Response monitoring and resistance prediction with positron emission tomography and tumor characteristics (REPOSIT): Study protocol of a phase II, open-label, multicenter study

Author

van der Hiel, Bernies, Haanen, John B A G, Stokkel, Marcel P M, Peeper, Daniel S., Jimenez, Connie R., Beijnen, Jos H, van de Wiel, Bart A., Boellaard, Ronald, van den Eertwegh, Alfons J M, van Tinteren, H., Wessels, Lodewyk F A, Lolkema, Martijn P J K, Hoekstra, Otto S, Hospers, Geke A P, Brouwers, Adrienne H, Koornstra, R.H.T., Arens, A. I. J., de Vos, F. Y.F.L., Hobbelink, M. G.G., Kapiteijn, H. W., de Geus-Oei, L. F., Kruit, W. H.J., Verzijlbergen, F.J., Aarts, M. J.B., Mottaghy, F. M., de Groot, J. W.B., Knollema, S., Piersma, D., Agool, A., Vreugdenhil, Art, Liem, I H, van den Berkmortel, Franchette W P J, Schreurs, M.W., and REPOSIT study group

Subjects
F-FLT, BRAF inhibitor, MEK inhibitor, Cancer Research, Oncology, PET/CT, Resistance, F-FDG, Genetics, Journal Article, Stage IIIc/IV melanoma
Abstract

Background: In patients with BRAFV600 mutated unresectable stage IIIc or metastatic melanoma, molecular targeted therapy with combined BRAF/MEK-inhibitor vemurafenib plus cobimetinib has shown a significantly improved progression-free survival and overall survival compared to treatment with vemurafenib alone. Nevertheless, the majority of BRAFV600 mutation-positive melanoma patients will eventually develop resistance to treatment. Molecular imaging with 18F-Fluorodeoxyglucose (18F-FDG) PET has been used to monitor response to vemurafenib in some BRAFV600 mutated metastatic melanoma patients, showing a rapid decline of 18F-FDG uptake within 2 weeks following treatment. Furthermore, preliminary results suggest that metabolic alterations might predict the development of resistance to treatment. 18F-Fluoro-3'-deoxy-3'L-fluorothymidine (18F-FLT), a PET-tracer visualizing proliferation, might be more suitable to predict response or resistance to therapy than 18F-FDG. Methods: This phase II, open-label, multicenter study evaluates whether metabolic response to treatment with vemurafenib plus cobimetinib in the first 7 weeks as assessed by 18F-FDG/18F-FLT PET can predict progression-free survival and whether early changes in 18F-FDG/18F-FLT can be used for early detection of treatment response compared to standard response assessment with RECISTv1.1 ceCT at 7 weeks. Ninety patients with BRAFV600E/K mutated unresectable stage IIIc/IV melanoma will be included. Prior to and during treatment all patients will undergo 18F-FDG PET/CT and in 25 patients additional 18F-FLT PET/CT is performed. Histopathological tumor characterization is assessed in a subset of 40 patients to unravel mechanisms of resistance. Furthermore, in all patients, blood samples are taken for pharmacokinetic analysis of vemurafenib/cobimetinib. Outcomes are correlated with PET/CT-imaging and therapy response. Discussion: The results of this study will help in linking PET measured metabolic alterations induced by targeted therapy of BRAFV600 mutated melanoma to molecular changes within the tumor. We will be able to correlate both 18F-FDG and 18F-FLT PET to outcome and decide on the best modality to predict long-term remissions to combined BRAF/MEK-inhibitors. Results coming from this study may help in identifying responders from non-responders early after the initiation of therapy and reveal early development of resistance to vemurafenib/cobimetinib. Furthermore, we believe that the results can be fundamental for further optimizing individual patient treatment. Trial registration:Clinicaltrials.govidentifier: NCT02414750. Registered 10 April 2015, retrospectively registered.

Published
2017

50. In the mix: the potential benefits of adding GM-CSF to CpG-B in the local treatment of patients with early-stage melanoma.

Author

Koster, Bas D., de Jong, Tamarah D., van den Hout, Mari F. C. M., Sluijter, Berbel J. R., Vuylsteke, Ronald J. C. L. M., Molenkamp, Barbara G., Vosslamber, Saskia, van den Tol, M. Petrousjka, van den Eertwegh, Alfons J. M., and de Gruijl, Tanja D.

Subjects
MELANOMA, IMMUNOREGULATION, SENTINEL lymph nodes
Abstract

Whereas TLR9 agonists are recognized as powerful stimulators of antitumor immunity, GM-CSF has had mixed reviews. In previously reported randomized trials we assessed the effects of local immune modulation in early-stage melanoma with CpG-B alone or with GM-CSF. Here we discuss the added value of GM-CSF and show sex-related differences. [ABSTRACT FROM AUTHOR]

Published
2020
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results