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
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