Please use this identifier to cite or link to this item:
Authors: Stege, Henner M.
Haist, Maximilian
Schultheis, S.
Fleischer, Maria Isabel
Mohr, Peter
Ugurel, Selma
Terheyden, Patrick
Thiem, Alexander
Kiecker, Felix
Leiter, Ulrike
Becker, Jürgen C.
Meissner, Markus
Kleeman, J.
Pföhler, Claudia
Hassel, Jessica
Grabbe, Stephan
Loquai, Carmen
Title: Response durability after cessation of immune checkpoint inhibitors in patients with metastatic Merkel cell carcinoma : a retrospective multicenter DeCOG study
Online publication date: 23-Aug-2022
Year of first publication: 2021
Language: english
Abstract: 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.
DDC: 610 Medizin
610 Medical sciences
Institution: Johannes Gutenberg-Universität Mainz
Department: FB 04 Medizin
Place: Mainz
Version: Published version
Publication type: Zeitschriftenaufsatz
License: CC BY
Information on rights of use:
Journal: Cancer immunology immunotherapy
Pages or article number: 3313
Publisher: Springer
Publisher place: Berlin u.a.
Issue date: 2021
ISSN: 1432-0851
Publisher DOI: 10.1007/s00262-021-02925-4
Appears in collections:JGU-Publikationen

Files in This Item:
  File Description SizeFormat
response_durability_after_ces-20220822135814380.pdf1.09 MBAdobe PDFView/Open