Response durability after cessation of immune checkpoint inhibitors in patients with metastatic Merkel cell carcinoma: a retrospective multicenter DeCOG study
Autor: | Jürgen C. Becker, Stephan Grabbe, Ulrike Leiter, Henner Stege, Claudia Pföhler, Peter Mohr, Jessica C. Hassel, Carmen Loquai, S. Schultheis, Felix Kiecker, S. Ugurel, Maximilian Haist, Patrick Terheyden, Markus Meissner, Maria Isabel Fleischer, J. Kleeman, A. Thiem |
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Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
Oncology Male Cancer Research medicine.medical_specialty Skin Neoplasms Rechallenge of immune checkpoint inhibitors Immunology Medizin 610 Medizin Duration of response Cohort Studies 03 medical and health sciences Immune checkpoint inhibitors 0302 clinical medicine 610 Medical sciences Internal medicine medicine Immunology and Allergy Humans Adverse effect Aged Retrospective Studies Aged 80 and over Merkel cell carcinoma business.industry Melanoma Middle Aged medicine.disease Metastatic Merkel cell carcinoma Discontinuation Carcinoma Merkel Cell 030104 developmental biology Treatment Outcome Tumor progression 030220 oncology & carcinogenesis Cohort Disease Progression Original Article Female Skin cancer Neoplasm Recurrence Local business Progressive disease Treatment cessation |
Zdroj: | Cancer Immunology, Immunotherapy |
ISSN: | 1432-0851 0340-7004 |
Popis: | Background Immune checkpoint inhibitors (ICI) have led to a prolongation of progression-free and overall survival in patients with metastatic Merkel cell carcinoma (MCC). However, immune-mediated adverse events due to ICI therapy are common and often lead to treatment discontinuation. The response duration after cessation of ICI treatment is unknown. Hence, this study aimed to investigate the time to relapse after discontinuation of ICI in MCC patients. Methods We analyzed 20 patients with metastatic MCC who have been retrospectively enrolled at eleven skin cancer centers in Germany. These patients have received ICI therapy and showed as best overall response (BOR) at least a stable disease (SD) upon ICI therapy. All patients have discontinued ICI therapy for other reasons than disease progression. Data on treatment duration, tumor response, treatment cessation, response durability, and tumor relapse were recorded. Results Overall, 12 of 20 patients (60%) with MCC relapsed after discontinuation of ICI. The median response durability was 10.0 months. Complete response (CR) as BOR to ICI-treatment was observed in six patients, partial response (PR) in eleven, and SD in three patients. Disease progression was less frequent in patients with CR (2/6 patients relapsed) as compared to patients with PR (7/11) and SD (3/3), albeit the effect of initial BOR on the response durability was below statistical significance. The median duration of ICI therapy was 10.0 months. Our results did not show a correlation between treatment duration and the risk of relapse after treatment withdrawal. Major reasons for discontinuation of ICI therapy were CR (20%), adverse events (35%), fatigue (20%), or patient decision (25%). Discontinuation of ICI due to adverse events resulted in progressive disease (PD) in 71% of patients regardless of the initial response. A re-induction of ICI was initiated in 8 patients upon tumor progression. We observed a renewed tumor response in 4 of these 8 patients. Notably, all 4 patients showed an initial BOR of at least PR. Conclusion Our results from this contemporary cohort of patients with metastatic MCC indicate that MCC patients are at higher risk of relapse after discontinuation of ICI as compared to melanoma patients. Notably, the risk of disease progression after discontinuation of ICI treatment is lower in patients with initial CR (33%) as compared to patients with initial PR (66%) or SD (100%). Upon tumor progression, re-induction of ICI is a feasible option. Our data suggest that the BOR to initial ICI therapy might be a potential predictive clinical marker for a successful re-induction. |
Databáze: | OpenAIRE |
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