Lack of Clinically Significant Relationships of Age or Body Mass Index with Merkel Cell Carcinoma Immunotherapy Outcomes

Abstract

Merkel cell carcinoma (MCC) is a rare and aggressive skin cancer with a high risk of metastasis. The development of anti-PD-1/PD-L1 immunotherapy has improved outcomes for advanced MCC, yet about 50% of such patients do not achieve durable responses. This study analyzed the effects of age and body mass index (BMI) on immunotherapy response in 183 advanced MCC patients from a single-center longitudinal database. Using Fine-Gray or Cox regression models, treatment response, progression-free survival (PFS), MCC-specific survival, and overall survival (OS) were evaluated. Age showed a significant non-linear relationship with treatment response (p = 0.04), with patients much older or younger than 70 years less likely to respond. However, age was not significantly associated with PFS (p = 0.21), MCC-specific survival (p = 0.72), or OS (p = 0.36). Similarly, BMI was not significantly correlated with treatment response (p = 0.41), PFS (p = 0.52), MCC-specific survival (p = 0.78), or OS (p = 0.71). Unlike previous studies suggesting that obesity and advanced age improve outcomes in other cancers, these associations were not observed in MCC. These findings suggest that age and BMI should not influence eligibility for immunotherapy in MCC patients, emphasizing the importance of unbiased patient selection for this treatment.

Keywords: Merkel cell carcinoma; age; body mass index; immunotherapy.

Figure 1

Impact of age and body mass index on immunotherapy outcomes relative to the median. In this cohort, progression-free survival (PFS) was defined as the time from IMTX initiation to either progressive disease, recurrence, or death. Objective response was determined as either CR or PR from the time of IMTX initiation. Age was treated as a non-linear variable for objective response, but as a linear variable for PFS and MCC-specific survival. Body mass index (BMI), Eastern Cooperative Oncology Group (ECOG) score, gender, stage, and immunosuppression status were all accounted for. The gray shaded area indicates the confidence interval. The median age was 70, with a first and third quartile value of 64 and 75, respectively. The median BMI was 30, with a first and third quartile value of 25.9 and 32.7, respectively. Black stars have been used to indicate quartile values, with the black dotted lines representing the medians. (A) shows that patients younger or older than the median age of 70 are less likely to achieve objective responses (p = 0.04). (B) shows that age is not significantly correlated with progression-free survival (p = 0.21). (C) also shows that age is not significantly correlated with MCC-specific survival (p = 0.72). (D–F) show that BMI is not significantly correlated with objective response, progression-free survival, or MCC-specific survival (p = 0.41, 0.52, and 0.78, respectively). CR = complete response; PR = partial response; IMTX = immunotherapy.