MERLIN_001 Trial: Gene Expression Testing Can Guide Melanoma Sentinel Lymph Node Biopsy
Sentinel lymph node biopsy (SLNB) is currently recommended for melanoma patients with tumors at least 0.8 mm thick and a 10% or greater risk of lymph node spread. Many cancer centers, including Moffitt, use SLNB for otherwise healthy patients with a 5% risk or greater, but for older or more frail patients they may use the 10% cutoff. The SLNB procedure gives doctors important staging information that helps guide treatment decisions and follow-up care.
About 20% of patients have cancer identified in their SLNB. This means that more than 80% of patients who have SLNB are found not to have cancer in their lymph nodes. If surgeons could better identify those patients, they could limit the number of people who undergo the surgery, which, although relatively safe, still involves associated risks, costs, and recovery time.
The landmark MERLIN_001 trial investigated whether a gene expression test could better predict which patients truly need SLNB. The study’s prospective blinded data showed the Merlin CP-GEP test accurately stratifies melanoma patients by sentinel node metastasis risk, showing a greater than three-fold difference between High-Risk and Low-Risk groups.
Trial Background and Results
MERLIN_001 is the largest study ever done to investigate a melanoma gene test. The trial included 1,761 patients with early-stage melanoma who had SLNB according to current guidelines and also had the MERLIN clinicopathologic gene expression profile test (CP-GEP, SkylineDX) done in a blinded fashion. The investigators and the participating patients did not know the status of their test results, and the laboratory doing the test did not know the results of the surgery. Afterwards, the results were analyzed to determine the predictive value of the CP-GEP test.
Dr. Vernon Sondak, Chair of Moffitt's Cutaneous Oncology Program, was the national Principal Investigator and one of three lead authors for the study report, published in the journal JAMA Surgery. The study was conducted at nine major melanoma centers around the country and explored whether this molecular test could be more effective than current risk assessment methods, which rely mostly on the pathologist’s report of the initial melanoma biopsy. Moffitt surgeon Dr. Jonathan Zager and Moffitt dermatopathologist Dr. Jane Messina were also coauthors on the study report.
The results were encouraging. The test labeled 37% of patients as low risk. Of these low-risk patients, only 7.1% had cancer in their lymph nodes. This translated to a 92.9% accuracy rate for correctly identifying patients without lymph node spread. Among high-risk patients, 23.8% had positive lymph nodes, confirming that the test works well for risk stratification.
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1,761
Patients with Early-Stage Melanoma
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92.9%
Accuracy Rate for Correctly Identifying Patients with Lymph Node Sperad
How Does the Test Work?
The Merlin CP-GEP test model, developed by the Mayo Clinic and biotech company SkylineDx, combines clinicopathologic information with genetic analysis. It examines two clinical/pathological factors (tumor thickness from the melanoma biopsy and patient age) and an 8-gene expression profile from the tumor biopsy, to classify patients into the low-risk and high-risk categories.
This non-invasive approach gave more precise risk information than clinical factors alone. For certain early melanomas (T1a with high-risk features, T1b, or T2a), the test provided over 90% confidence that lymph node risk is below the 10% surgery threshold.
This study represents a major step forward in evaluating personalized melanoma care and will allow us to have more informed conversations with our patients about their surgical treatment options. This kind of knowledge ultimately allows patients and surgeons to make better decisions about when sentinel node biopsy should be part of the management of clinically localized melanoma. In appropriately selected patients, this test can add value for shared decision-making.
-Dr. Vernon Sondak,Lead Investigator and Chair of the Cutaneous Oncology Program at Moffitt
By reducing unnecessary SLNB for low-risk patients while more accurately identifying high-risk patients who need surgery, fewer patients would face surgical risks like infection, fluid buildup, or lymphedema when their chance of benefit is low.
Which Patients Benefit Most from the Merlin Test?
This study indicates that the Merlin test is most helpful for patients in whom a higher risk threshold (10% or greater) is appropriate, such as those with other illnesses in addition to their melanoma, and elderly patients.
It may not be pertinent for patients in whom a 5% risk is enough to recommend SLNB surgery.
For patients with intermediate-risk melanomas where clinical factors don't provide clear guidance, referring to Moffitt for Merlin testing can offer valuable additional information.
Referring patients for this testing provides objective risk data, making treatment conversations more concrete and evidence-based. It can be beneficial when patients are questioning whether they need SLNB.
The test allows surgeons to explore alternative, less aggressive treatment paths when appropriate. It can reduce unnecessary surgeries for truly low-risk patients while ensuring that high-risk patients receive appropriate surgical intervention, improving both patient outcomes and supporting thoughtful resource utilization.
If you have melanoma patients who could benefit from Merlin testing, consider referring them to Moffitt Cancer Center. With leading melanoma specialists, comprehensive genomic testing capabilities, and a multidisciplinary team approach, Moffitt provides the expertise and resources needed to deliver personalized melanoma care.
