Abstract
Significant progress has been made in the treatment of advanced Merkel cell carcinoma (MCC) by establishing immune checkpoint inhibitors (ICI). Tumor progression, durable response, or adverse events may lead to ICI discontinuation in MCC patients. If in these patients tumor progression occurs, the question remains if re-induction with ICI achieves renewed tumor response. This retrospective multicenter study evaluated patients in with re-induction of anti-PD-1/anti-PD-L1 therapy for advanced MCC. Clinical data were extracted at treatment initiation, tumor response, treatment cessation, and subsequent tumor response to re-induction. Eight patients from seven centers (mean age 67.8 years) were included. The median duration of initial therapy with anti-PD-1/anti-PD-L1 was 9.6 months (2–21 months). Two patients achieved complete response (CR), four patients partial response (PR), one patient stable disease (SD), while in one patient progressive disease (PD) occurred as best overall response (BOR) to ICI. Reason for discontinuation of ICI was PD in three patients and severe adverse events in five patients. Following a median anti-PD-1/anti-PD-L1 therapy-free interval of 9.5 months (3–18 months), re-induction with ICI therapy was initiated. Five of eight patients (62.5%) achieved an objective response upon re-induction, while in three patients, no response could be observed. Notably, adverse events, which had led to the discontinuation of the first ICI treatment line, were not observed upon re-induction. The initial response to immune checkpoint inhibitors seems to be an important marker for successful re-induction. Interestingly, adverse events leading to treatment discontinuation were not observed during re-induction.
Highlights
ResultsThe therapy of metastatic Merkel cell carcinoma (MCC) has undergone major changes in recent years
Introduction of anti-progressive disease (PD)-1/anti-PD-L1 revolutionized the treatment for metastatic MCC cumulating in a significant increase of overall and progression free survival
Even though treatment with anti-PD-1/anti-PD-L1 is generally tolerated, severe adverse events next to PD are the main reasons for discontinuation of therapy [4, 5]
Summary
The therapy of metastatic Merkel cell carcinoma (MCC) has undergone major changes in recent years. The remarkable success of ICI therapy for immunogenic tumor entities, such as malignant melanoma, encouraged clinical studies, in which ICI therapy was used for the treatment of metastatic MCC. These studies illustrated that ICI therapy shows a good initial response, while contributing to a significantly prolonged OS and PFS. Two research questions guided this study: Can re-induction ICI lead to a renewed tumor response, and how is ICI reinduction therapy tolerated, especially in patients under rechallenge, who had to stop their first treatment due to immune related side effects? Two research questions guided this study: Can re-induction ICI lead to a renewed tumor response, and how is ICI reinduction therapy tolerated, especially in patients under rechallenge, who had to stop their first treatment due to immune related side effects? To investigate these questions, we initiated a retrospective study on the outcome of patients under reinduction treatment with ICI
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