Key Risk Factors Affect Physicians’ Choice of Treatment in Melanoma


During a Targeted Oncology™ Case-Based Roundtable™ event, Evan J. Lipson, MD, and participants discussed when they would use monotherapy or doublet therapy in metastatic melanoma.

Evan J. Lipson, MD

Associate Professor of Oncology

Johns Hopkins Medicine

Baltimore, MD

Evan J. Lipson, MD

Associate Professor of Oncology

Johns Hopkins Medicine

Baltimore, MD


  • What is your experience with nivolumab plus relatlimab (Opdualag) for metastatic melanoma? What are your perceptions about this regimen?

EVAN J. LIPSON, MD: In the National Comprehensive Cancer Network guidelines, nivolumab [Opdivo] plus ipilimumab [Yervoy], nivolumab plus relatlimab, pembrolizumab [Keytruda], and nivolumab are all category 1.1 Pembrolizumab plus low-dose ipilimumab is a category 2b, although we do occasionally use that in the appropriate patient where you’re concerned about adverse events but they need the ipilimumab coverage. There is a revision in the footnotes talking about this issue of the increased toxicity in patients when you’re adding ipilimumab.

Have you had the opportunity yet to administer relatlimab/nivolumab in clinic as part of a trial or off the trial?

GARY TIAN, MD: I used off the trial when it was approved. I only used once so far. The patient was on adjuvant…pembrolizumab, with stage II melanoma. She progressed while she was on adjuvant PD-1 [therapy]…she’s 70 years old. I put her on combination [nivolumab/relatlimab]. Unfortunately, she quickly progressed. She tolerated it well, but within 2 or 3 months she died. It’s a sad situation, even stage II, but she didn’t respond to immunotherapy in the adjuvant setting. I put her on the combination with nivolumab/relatlimab and she still progressed and died. That’s my limited experience.

LIPSON: So you used it in the second-line, essentially. The patient had already had anti-PD-1 monotherapy, you gave her nivolumab/relatlimab, and there’s approximately a 9% to 12% response rate in the second line, so the odds were not in her favor, unfortunately.2 I’m sorry to hear about that outcome.

MICHAEL HEMPHILL, MD: I have heard of it but I haven’t given [nivolumab and] relatlimab yet.

LIPSON: Do you have any perceptions of the regimen, either based on any of the publications, presentations, or anything you’ve read?

HEMPHILL: Not yet.

RYAN CARR, MD: I have not had the opportunity to give it yet.

LIPSON: Any perception based on what you’ve read?

CARR: [My perception is] that it may be a bit more efficacious [than] monotherapy but less toxic than the [nivolumab/ipilimumab] doublet. Is it one of those things where you’re stuck in between? Is it better just to give the [nivolumab/ipilimumab] doublet? I guess we’ll find out, but those are my thoughts.

JIGAR SHAH, MD: I haven’t had a chance to use it.

LESTER PORTER, MD: My only time to use it was on a clinical study and it started about 2 years ago. I heard that the patient is now 2 years in complete remission with the melanoma with 1 metastasis and is now off of therapy.

LIPSON: That’s good to hear. How old was the patient, approximately?

PORTER: They were 65 years old.

LIPSON: When you’re thinking about frontline regimens for these patients with unresectable, metastatic, BRAF wild-type disease, how are you making decisions about whether to use pembrolizumab or nivolumab versus how to use nivolumab/ipilimumab or nivolumab/relatlimab?

WEI LIN, MD: If the patient had reasonable ECOG performance status but large disease burden and visceral involvement, I would typically recommend the doublet nivolumab/ipilimumab unless there’s a contraindication or some concern about adverse events. If the patient is very frail and also [has] questionable autoimmune disorder but is on a steroid, I might consider single agent. I don’t believe single-agent pembrolizumab or nivolumab alone is as effective as nivolumab/ipilimumab combination. Often, when we see these metastatic patients, we only have a 1-time chance. Disease can progress quickly.

LIPSON: Yeah, that ‘1 shot’ phenomenon is the most challenging where you feel like you have to hit it the first time; you don’t want to turn the heat up so high that they suffer a bad toxicity, but you don’t want to go so gently that you haven’t given them the benefit of the dual [therapies].

VICTOR GIAN, MD: [For] patients who have bad visceral metastatic disease and certainly symptomatic patients, I absolutely would use combination immunotherapy. I’ve had some terrible toxicities related to nivolumab/ipilimumab.

SCOTT HAAKE, MD: I always worry about my ability to salvage in the second-line setting. So, if the patient has a reasonable performance status, I like to use the doublet therapies.

CARR: My only rule is [using] doublet [nivolumab/ipilimumab] for brain metastases. Otherwise, it just depends on the patient. If somebody has low volume disease, lung-only [metastasis], and normal lactate dehydrogenase, I’m almost certainly going to give monotherapy unless they’re very young and motivated to get dual immunotherapy. If they’re 85 years old, then I may be more inclined to do single-agent monotherapy. But my only hard and fast rule is regarding brain metastases. It’s the doublet [nivolumab/ipilimumab]. Everything else is case-by-case basis.

Lipson: Yes, [I agree about] brain metastases. I can count on 1 hand the number of patients who have brain metastases and don’t end up getting dual therapy. Those are usually frail patients where instead, I’m using a single agent plus stereotactic radiosurgery because I think there’s no way they’ll handle bad toxicity. That’s the exception to the rule.


1. NCCN. Clinical practice guidelines in oncology. Cutaneous melanoma, version 2.2023. Accessed June 7, 2023.

2. Ascierto PA, Lipson EJ, Dummer R, et al. Nivolumab and relatlimab in patients with advanced melanoma that had progressed on anti-programmed death-1/programmed death ligand 1 therapy: results from the phase I/IIa RELATIVITY-020 trial. J Clin Oncol. 2023;41(15):2724-2735. doi:10.1200/JCO.22.02072

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