Nivolumab Combinations Debated for a Patient With Metastatic Melanoma

Hussein A. Tawbi, MD, PhD (Moderator)

Professor

Deputy Chair

Director of Personalized Cancer Therapy

Department of Melanoma Medical Oncology

Division of Cancer Medicine

The University of Texas MD Anderson Cancer Center

Houston, TX

CASE SUMMARY

• Twelve years ago, a 78-year-old man with a history of stage III melanoma underwent surgical resection.
  • Lymph node density (LND): positive for nodal involvement
  • The patient declined complete LND and adjuvant systemic therapy.
  • He remained active since his surgery and maintains regular follow-up.
• On present-day routine follow-up, the patient presented with moderate asthenia that is limiting his daily activities, without other relevant clinical symptoms.
• ECOG performance status: 1
• Physical examination: unremarkable
• Notable laboratory findings: lactate dehydrogenase 380 UI/L (reference range, 110-240)
• Full-body CT scan revealed the presence of pulmonary and hepatic nodules, 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.
  • Mutation testing: BRAF negative

DISCUSSION QUESTIONS

• Beyond the absence of an actionable BRAF mutation, what factors influence first-line selection of immunotherapy (IO) monotherapy versus dual IO therapy?

Hussein A. Tawbi, MD, PhD: Would anyone have considered IO monotherapy? What are the factors that you typically look at? And then, given that you've been choosing here between 2 combinations, what may have made you choose the ipilimumab [Yervoy]/nivolumab [Opdivo] vs nivolumab/relatlimab-rmbw [Opdualag]?

Maryada S. Reddy, MD: If a patient's performance status is not the best, that's one of the criteria. If they are elderly or frail, I may choose single-agent IO treatment. But this patient has an elevated lactate dehydrogenase level, liver disease and disease burden, and his performance status is 1.

Tawbi: Very reasonable. If you were thinking only about the patient's comorbidities and performance status, you might consider single agent, but in this case, you thought that the patient had a higher tumor burden. Did you choose ipilimumab/nivolumab or nivolumab/relatlimab for him? And normally, do you use the 3 mg/kg for ipilimumab [and 1 mg/kg] for nivolumab, or do you use the lower dose that's used for other cancers?

Reddy: I chose ipilimumab/nivolumab. We use the standard, what's approved for metastatic melanoma. We don't use the 1-mg dose [of ipilimumab] for melanoma.

Shan Guo, MD: We use 1 mg [of ipilimumab]. In the community, I have a lot of older and frail patients, so when I use ipilimumab, I tend to use a 1 mg/kg.

Tawbi: For the participants who chose nivolumab/relatlimab, I'm interested in your thoughts on why you would choose that for this patient or not.

Jyothy Dodlapati, MD: I chose that regimen. Efficacy wise, it's almost equivalent to ipilimumab/nivolumab, but without the immune adverse events of the ipilimumab. I chose nivolumab/relatlimab, but I could have gone either way. I could have gone with ipilimumab/nivolumab as well.

Tawbi: As someone who's helped develop this combination, I think all of your points are very well taken. None of those choices are necessarily wrong. In different settings, some of these factors are going to affect our decision making.

Brain metastases are also a common [development] in our patients with melanoma. In first-line [metastatic] melanoma, up to 40% of patients can have brain metastases. If we go all the way to end of life, up to 70% to 80% would have experienced brain metastasis along the way. Does that change which of the 2 combinations you would consider?

Dodlapati: In that case, ipilimumab/nivolumab.

Swetha Yadav, MD: If they're BRAF mutated, is ipilimumab/nivolumab a preferred combination IO option vs nivolumab/relatlimab?

Tawbi: That's a great question, and it's not clear. Ipilimumab/nivolumab vs nivolumab is a lot better for BRAF-mutated disease,¹ but for nivolumab/relatlimab, BRAF-mutated and BRAF wild-type look almost identical, so it still gets the benefit.²

REFERENCES:

1. Larkin J, Chiarion-Sileni V, Gonzalez R, et al. Five-year survival with combined nivolumab and ipilimumab in advanced melanoma. N Engl J Med. 2019;381(16):1535-1546. doi:10.1056/NEJMoa1910836

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