Immunotherapy response in immunosuppressed patients with Merkel cell carcinoma: analysis of 183 patients
March 27, 2025
Journal
BMJ Oncology
Publication Date
March 27, 2025
Authors
Merkelcell.org Summary
Immunotherapy helps the immune system fight cancer and is effective in about 60% of patients with advanced Merkel cell carcinoma (MCC). However, its effectiveness in patients with weakened immune systems (immunosuppressed patients) is less understood. Immunosuppression can happen due to conditions like organ transplants, HIV/AIDS, and autoimmune diseases.
This study compared immunotherapy outcomes in 147 MCC patients with healthy immune systems and 36 immunosuppressed patients. While immunosuppressed patients had a higher risk of their cancer worsening, immunotherapy was still effective for them — 50% responded within six months, compared to 62% of those with healthy immune systems. However, the response varied by the immunosuppressive condition they had. Patients with chronic lymphocytic leukemia (CLL) had poor outcomes, with only 20% responding and 80% having their cancer worsen within two years. Overall, immunosuppressed patients also had more side effects (52%) from immunotherapy than those with healthy immune systems (37%).
These findings suggest that while immunotherapy may not work as well for immunosuppressed MCC patients, it can still be beneficial and likely remains the best treatment option for many. However, more research is needed on why patients with certain conditions do not respond to immunotherapy, and how to improve outcomes for these patients.
Abstract
Objective
Merkel cell carcinoma (MCC) is an aggressive skin cancer with poor outcomes in immunosuppressed patients. While immune checkpoint inhibitors (ICIs) achieve ~60% response rates in immunocompetent MCC patients, their efficacy in immunosuppressed patients remains unclear due to exclusion from trials. This study compares ICI outcomes, safety and the impact of immunosuppression subtypes between these groups.
Methods and analysis
This retrospective study analysed 183 advanced MCC patients on first-line ICIs from a Seattle-based data repository. Of these, 147 were immunocompetent, and 36 were immunosuppressed (chronic lymphocytic leukaemia (CLL) n=10, autoimmune disorders n=10, other haematologic malignancies n=9, solid organ transplants n=4 and HIV/AIDS n=3). Outcomes included objective response rate, disease progression, MCC-specific and overall survival probability, adjusted for age, sex and stage at ICI initiation.
Results
Initial ICI response rates at 6 months were 50% in immunosuppressed and 61.5% in immunocompetent patients (HR=0.71, p=0.17). Immunosuppressed patients had higher risks of disease progression (2 years: 53.9% vs 42.1%, HR=1.65, p=0.05) and MCC-specific mortality (2 years: 38.7% vs 24.4%, HR=1.85, p=0.04). CLL patients (n=10) had a particularly low response rate (response rate: 20.0% vs 61.5%, HR=0.18, p=0.02) and high progression risk (2 years: 80.0% vs 42.1%, HR=4.09, p=0.01). Immunosuppressed patients faced higher rates of ICI toxicity (6-month risk: 51.6% vs 36.6%, HR=1.79, p=0.03).
Conclusions
ICIs provide meaningful benefits to immunosuppressed MCC patients, though their response rates are lower, and progression risk is higher compared with immunocompetent patients.