The Significance of Nivolumab Plus Relatlimab for Advanced Melanoma


Jason Luke, MD, discussed the role played by the combination of nivolumab plus relatlimab in patients with advanced melanoma.

Jason Luke, MD, associate professor of medicine in the Division of Hematology/Oncology and the director of the Cancer Immunotherapeutics Center at the University of Pittsburgh Medical Center Hillman Cancer Center, discussed the role played by the combination of nivolumab plus relatlimab (Opdualag) in patients with advanced melanoma.

The phase 3 RELATIVITY-047 trial (NCT03470922) randomly assigned patients to receive nivolumab plus relatlimab versus nivolumab alone (Opdivo). Relatlimab is an immune checkpoint inhibitor (ICI) that targets LAG-3, as opposed to other immune checkpoint inhibitors that have targeted PD-1/PD-L1 or CTLA-4. Luke says the use of a third immune checkpoint is potentially important beyond its use in patients with melanoma.

The results of the trial showed benefit to progression-free survival for the combination over nivolumab alone, leading to approval by the FDA. Luke said this impacts practice significantly, especially in lower-risk patients who would have otherwise received single-agent nivolumab or pembrolizumab (Keytruda).

For higher-risk patients with features including brain or liver metastases or high lactate dehydrogenase (LDH), Luke says he would use nivolumab plus ipilimumab (Yervoy), but in other patients who have received no prior systemic therapy, he would now give nivolumab plus relatlimab.


0:08 | RELATIVITY-047 was a phase 3 clinical trial demonstrating the benefit of combining nivolumab and relatlimab versus nivolumab alone. And this is a seminal clinical trial in oncology beyond just melanoma because this validates the third immune checkpoint to be used in standard-of-care practice. So that's important in melanoma obviously, as we have another treatment option for our patients, but it actually opens the door more broadly in oncology to see combination immunotherapy start to be used in other tumor types as well.

Focusing back on melanoma however, essentially, the way I think about it is that the data really support the use of Opdualag, nivolumab plus relatlimab, in the lower-risk patients who I would have otherwise treated with PD-1 monotherapy, meaning nivolumab or pembrolizumab. So when I see a new patient who is treatment naive, I go through my mind and think about, first, are there high-risk features here that would make me think I still want to give nivolumab plus ipilimumab? Those might be brain [metastases], liver [metastases], high LDH, etc. If the patient does not have those features, then my default is to give Opdualag, with nivolumab plus relatlimab, in most of these general-risk or low-risk patients that present in the treatment-naive setting.

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