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Brief Report
September 16, 2020

Incidence of New Primary Cutaneous Melanoma in Patients With Metastatic Melanoma Treated With Immune Checkpoint Inhibitors: A Single-Center Cohort Study

Author Affiliations
  • 1Dermatology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York
  • 2Department of Dermatology, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
  • 3Andreas Syggros Hospital of Skin and Venereal Diseases, Department of Dermatology, University of Athens, Athens, Greece
JAMA Dermatol. Published online September 16, 2020. doi:10.1001/jamadermatol.2020.3671
Key Points

Question  What is the incidence of new primary cutaneous melanoma (CM) after initiating immune checkpoint inhibitor therapy for metastatic melanoma?

Findings  In this single-center observational cohort study, 42 of 2251 patients (1.9%) who received immune checkpoint inhibitors were diagnosed with 48 melanomas. The incidence rate was approximately 1100 cases per 100 000 person-years, and the cumulative cause-specific risk of new CM after 5 years was 4.9%; patients diagnosed with a new primary CM were more likely to have a family history of melanoma.

Meaning  Patients who receive checkpoint inhibitors for treatment of metastatic melanoma remain at risk for the development of new primary CMs.


Importance  The development of new primary cutaneous melanoma (CM) after starting immune checkpoint inhibitor (ICI) therapy is poorly characterized.

Objective  To determine the incidence of new CM in patients treated with ipilimumab, nivolumab, and/or pembrolizumab for metastatic melanoma.

Design, Setting, and Participants  Single-center, retrospective, observational cohort study using an institutional database to identify patients diagnosed with melanoma at a tertiary care cancer hospital in New York, New York.

Exposures  Ipilimumab, nivolumab, and/or pembrolizumab treatment for metastatic melanoma.

Main Outcomes and Measures  Primary outcomes were the incidence proportion, the incidence rate, and the 5-year cause-specific cumulative risk.

Results  A total of 2251 patients were included in the study; mean (SD) age at the time of ICI start was 62.8 (14.4) years. The majority were male (63.8%, n = 1437), White (92.7%, n = 2086), and non-Hispanic (92.1%, n = 2073). Forty-two of 2251 patients who received ipilimumab, nivolumab, and/or pembrolizumab were diagnosed with 48 new CMs at a median (range) of 397.5 (39-2409) days after ICI initiation. The median age of affected patients at the time of ICI first dose was 66.5 years. The majority were male (66.7%, n = 28), White (92.9%, n = 39), and non-Hispanic (100.0%, n = 42). There were no differences in age, sex, race, and ethnicity among patients who did and did not develop a new CM. Patients who developed a new CM were more likely to have a family history of melanoma (23.8% vs 16.3%, P = .02). Most new CMs (n = 30, 62.5%) were diagnosed after the last date of ICI administration. Twenty-seven (56.3%) new CMs were in situ and 21 (43.8%) were invasive. Of the invasive CMs with a reported Breslow thickness (n = 20), the median (range) thickness was 0.4 (0.1-8.4) mm. The overall incidence proportion of new CM was 1.9% (95% CI, 1.4%-2.5%) and the incidence rate was 1103 cases per 100 000 person-years (95% CI, 815-1492). The 5-year cumulative cause-specific risk of new CM was 4.9% (95% CI, 3.3%-7.4%).

Conclusions and Relevance  Patients treated with ICI therapy for metastatic melanoma remain at risk for the development of new CM.

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    1 Comment for this article
    Incidence of primary melanoma in patients undergoing immunotherapy may be a reflection of melanoma overdiagnosis
    Robert Swerlick, MD | Emory University
    Patients undergoing treatment for metastatic melanoma experience a level of cutaneous melanoma surveillance at levels beyond the general population. The increase in melanoma frequency (>1100/100,000) may be explained by surveillance bias. Greater surveillance intensity almost invariably translates to increase frequency of disease detection, frequently with the detection of pseudo disease. Whether the pathological diagnosis of melanoma discerned under these conditions has any biologic meaning is question, especially when the patients in this population are undergoing successful treatment of a much larger tumor burden of metastatic disease. This makes no biologic sense.