Background Patients with stage IB-IIA cutaneous melanoma (CM) account for approximately one quarter of all patients with melanoma, have 20–38% recurrence rates, and 6–12% melanoma-specific mortality rates by 10 years,1 2 but they are not eligible for adjuvant immunotherapy. By comparison, immunotherapy is approved for adjuvant treatment of patients with stage IIB CM. Molecular testing of stage IB-IIA patients with the 31-GEP test can identify patients who have a risk of recurrence similar to that seen for stage IIB patients and may benefit from immunotherapy. The 31-gene expression profile test (31-GEP) stratifies patients into low (Class 1A), intermediate (Class 1B/2A), or high (Class 2B) risk of recurrence, metastasis, and death.
Methods Patients with stage IB-IIA (n=673) and IIB (n=174) CM from previously published prospective and retrospective studies (N=847) were analyzed by the 31-GEP.3–8 Five-year RFS and MSS risk stratification was assessed using Kaplan-Meier analysis with the log-rank test.
Results The 31-GEP stratified 5-year RFS among patients with stage IB-IIA CM (Class 1A=91.8% vs. Class 1B/2A=85.1% vs. Class 2B=64.2%, p<0.001) and those with stage IIB CM (Class 1A=75.0% vs. Class 1B/2A=78.4% vs. Class 2B=55.4%, p=0.02). The 31-GEP also significantly stratified 5-year MSS for those with stage IB-IIA CM (Class 1A=99.2% vs. Class 1B/2A=96.9% vs. Class 2B=87.6%, p<0.001) and those with stage IIB CM (Class 1A=100% vs. Class 1B/2A=94.9% vs. Class 2B=90.4%, p=0.02). Multivariable analysis with the 31-GEP (Class 1A, Class 1B/2A, and Class 2B) and AJCC stage (IB vs. IIA) found that, among stage IB-IIA patients, Class 1B/2A (HR=1.72, p=0.048), Class 2B (HR=3.33, p<0.001), and stage IIA (HR=1.84, p=0.006) were significant predictors of recurrence. Only the 31-GEP Class 2B result was a significant predictor of melanoma-specific mortality in multivariable analysis for patients with stage IB-IIA CM (HR=7.90, p<0.001).
Conclusions In patients with stage IB-IIA CM, the 31-GEP identified those with a high risk of recurrent disease (64.2% 5-year RFS for Class 2B), which was like that of stage IIB CM (63.4% overall 5-year RFS), for whom adjuvant therapy is approved. The 31-GEP provided significant risk stratification for both recurrence and melanoma-specific mortality in patients with stage IB-IIA CM, a group that can have a nearly 40% recurrence rate but is not currently eligible for adjuvant immunotherapies. The 31-GEP provides personalized, independent risk stratification, which enhances adjuvant therapy selection in future clinical trials in this population.
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Ethics Approval Each cohort included in the analysis received institutional review board approval at the affiliated institutional IRB.
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