Immunotherapy Options for an Older Patient With Metastatic Melanoma

April K.S. Salama, MD

Associate Professor of Medicine

Duke University School of Medicine

Durham, NC

CASE SUMMARY

A 78-year-old man with a history of stage III melanoma underwent surgical resection 12 years ago; his lymph node dissection (LND) was positive for nodal involvement. The patient declined complete LND and adjuvant systemic therapy. He remained active since his surgery and maintained regular follow-up appointments.

On routine follow-up, the patient presented with moderate asthenia that limited his daily activities. His ECOG performance status was 1, and his physical examination was unremarkable. Notable laboratory findings included lactate dehydrogenase (LDH) level of 380 U/L (reference range, 110-240 U/L). A full-body CT scan revealed pulmonary and hepatic nodules but no evidence of brain metastases. He underwent core-needle biopsy of the largest hepatic lesion in segment IVb without any complications. Pathology revealed metastatic melanoma.

APRIL K.S. SALAMA, MD: If this patient was in your clinic with previously untreated metastatic melanoma, we have lots of choices. It’s a good problem to have as an oncologist treating melanoma these days. Based on the factors, this is a patient without brain metastases, but with distant visceral disease. I’m curious to see what you would offer this 78-year-old patient. It seems the choices were primarily split between the dual checkpoint inhibitor therapies, with some PD-1 inhibitor monotherapy.

LAWRENCE NEGRET, MD: I would probably use nivolumab [Opdivo] plus ipilimumab [Yervoy]. I think that’s still the preferred regimen, but I may consider, from his age, using low-dose ipilimumab with higher-dose nivolumab.¹ There are some data now that show you can use nivolumab/relatlimab [Opdualag] once they fail nivolumab/ipilimumab.² It gives you a second-line option. That’s the way I would probably approach it. I’ve used more of the alternate dosing because of age, but I still think nivolumab/ipilimumab is the preferred [regimen].

FRANTZ FRANCISQUE, MD: I [would choose] nivolumab/relatlimab because the data are similar compared with nivolumab/ipilimumab and the tolerability is slightly better.^2,3 If I use nivolumab/ipilimumab, which I think is a good choice and the first choice, I would use nivolumab/relatlimab in the second line. But I tend to lean towards it more because…compared with nivolumab/ipilimumab, the data are similar or better.

SALAMA: That’s a great point, weighing the relative benefit and toxicity and certain patient factors.

PHU TRAN, MD: I have usually used nivolumab/ipilimumab in the past, but now seeing the approval of nivolumab/relatlimab I [would] switch over. The tolerability is, in my experience, a lot better than the nivolumab/ipilimumab combination. I rarely have any patient have any significant adverse event like diarrhea or severe colitis that require [hospital] admission. So far, [my patients] all seem to get pretty good responses, including 1 who had a complete response. So far, it’s a very good experience for me.

SALAMA: That’s good to hear.

JORGE HURTADO, MD: I will primarily use nivolumab/ipilimumab. There are some data also that you can restage the patient after 2 cycles.⁴ If there hasn’t been a response, you can drop the ipilimumab because the likelihood of response will be a lot less. But I will give a chance to nivolumab/ipilimumab based on the [slightly] superior response rate [vs nivolumab/relatlimab], and more maturity of the data.^2,3

SALAMA: Good points. I think everyone’s made the points that we’re all thinking about, trying to weigh risk and benefit when we’re making decisions in clinic.

DISCUSSION QUESTION

• Beyond the absence of an actionable BRAF mutation, what factors influence the first-line selection of immune monotherapy versus dual immunotherapy in a patient such as this?

SALAMA: It seems like this is a group that is in favor of a dual checkpoint inhibitor therapy. What are the factors that go into your decision making for monotherapy vs dual immunotherapy? We’ve listed some things that we take into account, but how you make these decisions?

In my own practice, it certainly mirrors what many people here have talked about, favoring dual checkpoint inhibitor therapy…. The group that we now treat with monotherapy has become less and less common, based on some of the data. Although I think there are certain situations where monotherapy still may be warranted. Comorbidities…for example, underlying autoimmune disorders or other things where we might be worried about an increased risk of adverse events, depending on site of disease and extent of disease. Age of the patient can sometimes influence that. I’ve personally treated a few patients well into their 90s, and that’s an extreme example. Those are patients where I may be more likely to use monotherapy vs dual checkpoint inhibitor therapy.

TRAN: In the past, in patients who are frail, I would lean toward monotherapy, like pembrolizumab [Keytruda]. I think nivolumab/relatlimab is, from my experience, very tolerable so I’m leaning toward that direction now.

NEGRET: [With] high LDH or higher tumor burden, I’m even more willing to do dual immunotherapy. Also, I think if they have the BRAF mutation, they seem to do better if they have dual immunotherapy. There are some data saying that.²

SALAMA: Yes, there are [data] on different subgroups.

NEGRET: So if they’re wild-type, have low LDH, have low tumor burden, or they’re older, you might consider monotherapy more in that type of patient. But in general, default is the doublet unless somebody needs monotherapy for those other reasons that you state [such as] comorbidities.

SALAMA: That’s a great point. We could talk for hours on why there’s not a biomarker for selecting immunotherapy, [but] I don’t use PD-L1 or LAG-3 expression in melanoma. PD-L1 expression is predictive, but it’s not adequate to select 1 type of therapy over another. It sounds like most [physicians] are not using that, which is good to hear.

_References:

_{1. Lebbe C, Meyer N, Mortier L, et al. Two dosing regimens of nivolumab (NIVO) plus ipilimumab (IPI) for advanced (adv) melanoma: Three-year results of CheckMate 511. J Clin Oncol. 2021;39(suppl 15):9516. doi:10.1200/JCO.2021.39.15_suppl.9516}

_{2. Tawbi HA, Schadendorf D, Lipson EJ, et al. Relatlimab and nivolumab versus nivolumab in untreated advanced melanoma. N Engl J Med. 2022;386(1):24-34. doi:10.1056/NEJMoa2109970}

_{3. Wolchok JD, Chiarion-Sileni V, Gonzalez R, et al. Long-term outcomes with nivolumab plus ipilimumab or nivolumab alone versus ipilimumab in patients with advanced melanoma. J Clin Oncol. 2022;40(2):127-137. doi:10.1200/JCO.21.02229}

_{4. Postow MA, Goldman DA, Shoushtari AN, et al. Adaptive dosing of nivolumab + ipilimumab immunotherapy based upon early, interim radiographic assessment in advanced melanoma (The ADAPT-IT Study). J Clin Oncol. 2022;40(10):1059-1067. doi:10.1200/JCO.21.01570}