Low-Dose Nivolumab with or without Ipilimumab as Adjuvant Therapy Following the Resection of Melanoma Metastases: A Sequential Dual Cohort Phase II Clinical Trial
Background: Optimal dosing and duration of adjuvant treatment with PD-1 and CTLA-4 immune checkpoint inhibitors have not been established. Prior to their regulatory approval we investigated a low-dose regimen of nivolumab with or without ipilimumab in a sequential dual-cohort phase II clinical trial...
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MDPI AG
2022-01-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/14/3/682 |
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| author | Julia Katharina Schwarze Soizic Garaud Yanina J. L. Jansen Gil Awada Valérie Vandersleyen Jens Tijtgat Alexandre de Wind Paulus Kristanto Teofila Seremet Karen Willard-Gallo Bart Neyns |
| author_facet | Julia Katharina Schwarze Soizic Garaud Yanina J. L. Jansen Gil Awada Valérie Vandersleyen Jens Tijtgat Alexandre de Wind Paulus Kristanto Teofila Seremet Karen Willard-Gallo Bart Neyns |
| author_sort | Julia Katharina Schwarze |
| collection | DOAJ |
| description | Background: Optimal dosing and duration of adjuvant treatment with PD-1 and CTLA-4 immune checkpoint inhibitors have not been established. Prior to their regulatory approval we investigated a low-dose regimen of nivolumab with or without ipilimumab in a sequential dual-cohort phase II clinical trial. Methods: Following the complete resection of melanoma metastases, patients were treated with a single fixed dose of ipilimumab (50 mg) plus 4 bi-weekly fixed doses of nivolumab (10 mg) (cohort-1), or nivolumab for 1 year (10 mg fixed dose, Q2w x9, followed by Q8w x4) (cohort-2). Twelve-months relapse-free survival (RFS) served as the primary endpoint. Results: After a median follow-up of 235 weeks for cohort-1 (34 patients), and 190 weeks for cohort-2 (21 patients), the 12-months RFS-rate was, respectively, 55.9% (95% CI, 39–72), and 85.7% (95% CI, 70–100). Treatment-related adverse events occurred in 27 (79%), and 18 (86%) patients, with 3 (9%), and 1 (5%) grade 3 adverse events in cohort-1 and -2, respectively. Immunohistochemical quantification of intra- and peritumoral CD3<sup>+</sup> T cells and CD20<sup>+</sup> B cells, but not PD-1/PD-L1 staining, correlated significantly with RFS. Conclusions: One year of adjuvant low-dose nivolumab could be an effective and economically advantageous alternative for standard dosing, at the condition of further confirmation in a larger patient cohort. A shorter low-dose nivolumab plus ipilimumab regimen seems inferior and less tolerable. |
| first_indexed | 2024-03-10T00:07:45Z |
| format | Article |
| id | doaj.art-f5ca751d91cf482496d6b73b0ffe754f |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T00:07:45Z |
| publishDate | 2022-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-f5ca751d91cf482496d6b73b0ffe754f2023-11-23T16:06:59ZengMDPI AGCancers2072-66942022-01-0114368210.3390/cancers14030682Low-Dose Nivolumab with or without Ipilimumab as Adjuvant Therapy Following the Resection of Melanoma Metastases: A Sequential Dual Cohort Phase II Clinical TrialJulia Katharina Schwarze0Soizic Garaud1Yanina J. L. Jansen2Gil Awada3Valérie Vandersleyen4Jens Tijtgat5Alexandre de Wind6Paulus Kristanto7Teofila Seremet8Karen Willard-Gallo9Bart Neyns10Department of Medical Oncology, Vrije Universiteit Brussel (VUB)/Universitair Ziekenhuis Brussel (UZ Brussel), Laarbeeklaan 101, 1090 Brussels, BelgiumMolecular Immunology Unit, Institut Jules Bordet, Université Libre de Bruxelles, 1000 Brussels, BelgiumDepartment of Thoracic Surgery, Vrije Universiteit Brussel (VUB)/Universitair Ziekenhuis Brussel (UZ Brussel), Laarbeeklaan 101, 1090 Brussels, BelgiumDepartment of Medical Oncology, Vrije Universiteit Brussel (VUB)/Universitair Ziekenhuis Brussel (UZ Brussel), Laarbeeklaan 101, 1090 Brussels, BelgiumDepartment of Medical Oncology, Vrije Universiteit Brussel (VUB)/Universitair Ziekenhuis Brussel (UZ Brussel), Laarbeeklaan 101, 1090 Brussels, BelgiumDepartment of Medical Oncology, Vrije Universiteit Brussel (VUB)/Universitair Ziekenhuis Brussel (UZ Brussel), Laarbeeklaan 101, 1090 Brussels, BelgiumDepartment of Pathology, Institut Jules Bordet, Université Libre de Bruxelles, 1000 Brussels, BelgiumData Center, Institut Jules Bordet, Université Libre de Bruxelles, 1000 Brussels, BelgiumDepartment of Medical Oncology, Vrije Universiteit Brussel (VUB)/Universitair Ziekenhuis Brussel (UZ Brussel), Laarbeeklaan 101, 1090 Brussels, BelgiumDepartment of Thoracic Surgery, Vrije Universiteit Brussel (VUB)/Universitair Ziekenhuis Brussel (UZ Brussel), Laarbeeklaan 101, 1090 Brussels, BelgiumDepartment of Medical Oncology, Vrije Universiteit Brussel (VUB)/Universitair Ziekenhuis Brussel (UZ Brussel), Laarbeeklaan 101, 1090 Brussels, BelgiumBackground: Optimal dosing and duration of adjuvant treatment with PD-1 and CTLA-4 immune checkpoint inhibitors have not been established. Prior to their regulatory approval we investigated a low-dose regimen of nivolumab with or without ipilimumab in a sequential dual-cohort phase II clinical trial. Methods: Following the complete resection of melanoma metastases, patients were treated with a single fixed dose of ipilimumab (50 mg) plus 4 bi-weekly fixed doses of nivolumab (10 mg) (cohort-1), or nivolumab for 1 year (10 mg fixed dose, Q2w x9, followed by Q8w x4) (cohort-2). Twelve-months relapse-free survival (RFS) served as the primary endpoint. Results: After a median follow-up of 235 weeks for cohort-1 (34 patients), and 190 weeks for cohort-2 (21 patients), the 12-months RFS-rate was, respectively, 55.9% (95% CI, 39–72), and 85.7% (95% CI, 70–100). Treatment-related adverse events occurred in 27 (79%), and 18 (86%) patients, with 3 (9%), and 1 (5%) grade 3 adverse events in cohort-1 and -2, respectively. Immunohistochemical quantification of intra- and peritumoral CD3<sup>+</sup> T cells and CD20<sup>+</sup> B cells, but not PD-1/PD-L1 staining, correlated significantly with RFS. Conclusions: One year of adjuvant low-dose nivolumab could be an effective and economically advantageous alternative for standard dosing, at the condition of further confirmation in a larger patient cohort. A shorter low-dose nivolumab plus ipilimumab regimen seems inferior and less tolerable.https://www.mdpi.com/2072-6694/14/3/682adjuvantmelanomaimmunotherapylow dosenivolumabipilimumab |
| spellingShingle | Julia Katharina Schwarze Soizic Garaud Yanina J. L. Jansen Gil Awada Valérie Vandersleyen Jens Tijtgat Alexandre de Wind Paulus Kristanto Teofila Seremet Karen Willard-Gallo Bart Neyns Low-Dose Nivolumab with or without Ipilimumab as Adjuvant Therapy Following the Resection of Melanoma Metastases: A Sequential Dual Cohort Phase II Clinical Trial Cancers adjuvant melanoma immunotherapy low dose nivolumab ipilimumab |
| title | Low-Dose Nivolumab with or without Ipilimumab as Adjuvant Therapy Following the Resection of Melanoma Metastases: A Sequential Dual Cohort Phase II Clinical Trial |
| title_full | Low-Dose Nivolumab with or without Ipilimumab as Adjuvant Therapy Following the Resection of Melanoma Metastases: A Sequential Dual Cohort Phase II Clinical Trial |
| title_fullStr | Low-Dose Nivolumab with or without Ipilimumab as Adjuvant Therapy Following the Resection of Melanoma Metastases: A Sequential Dual Cohort Phase II Clinical Trial |
| title_full_unstemmed | Low-Dose Nivolumab with or without Ipilimumab as Adjuvant Therapy Following the Resection of Melanoma Metastases: A Sequential Dual Cohort Phase II Clinical Trial |
| title_short | Low-Dose Nivolumab with or without Ipilimumab as Adjuvant Therapy Following the Resection of Melanoma Metastases: A Sequential Dual Cohort Phase II Clinical Trial |
| title_sort | low dose nivolumab with or without ipilimumab as adjuvant therapy following the resection of melanoma metastases a sequential dual cohort phase ii clinical trial |
| topic | adjuvant melanoma immunotherapy low dose nivolumab ipilimumab |
| url | https://www.mdpi.com/2072-6694/14/3/682 |
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