First-line immune checkpoint inhibitors have improved survival in patients with metastatic melanoma but remain underused in this population, according to research published in JAMA Network Open.

The study showed that first-line immune checkpoint inhibitor use increased from 2010 to 2019, but 38% of patients were not receiving first-line immune checkpoint inhibitors in 2019. 

The study included 16,831 adults 20 years of age and older who were newly diagnosed with stage IV cutaneous melanoma from 2010 to 2019. The vast majority of patients were non-Hispanic White (93.6%), and most were men (67.9%). 

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First-line use of immune checkpoint inhibitors increased from 8.9% in 2010 to 38.8% in 2015 and 62.5% in 2019. The median overall survival (OS) for all patients improved from 7.7 months in 2010 to 17.5 months in 2018. 

To assess the association between first-line immune checkpoint inhibitor use and OS, the researchers looked at patients diagnosed in 2016 or later (due to the timing of regulatory approval). To account for immortal time bias in receiving immune checkpoint inhibitors, the researchers used landmark time points — 48 days or 78 days from diagnosis to the start of immune checkpoint inhibitor treatment.

Using either landmark time point, OS was significantly improved with first-line immune checkpoint inhibitor use, even after the researchers adjusted for patient, disease, and treatment factors. 

When the researchers used the 78-day time point, the median OS was 43.7 months in patients who received immune checkpoint inhibitors and 16.1 months in patients who received other first-line systemic therapy (adjusted hazard ratio, 0.72; 99% CI, 0.62-0.85; P <.001). The 3-year OS rate was 53.0% and 35.5%, respectively. 

In all, 55.9% of patients received first-line immune checkpoint inhibitor therapy from 2016 to 2019. Patients were less likely to receive immune checkpoint inhibitors if they were 80 years of age or older, had Medicaid, lived in zip codes with lower median household incomes, presented with brain metastasis, did not receive first-line radiation, or were diagnosed at community hospitals.

Disclosures: One study author declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Lamba N, Ott PA, Iorgulescu JB. Use of first-line immune checkpoint inhibitors and association with overall survival among patients with metastatic melanoma in the anti–PD-1 era. JAMA Netw Open. Published online August 25, 2022. doi:10.1001/jamanetworkopen.2022.25459