Success in First Real-World Case of Relatlimab Combo for Treatment of Conjunctival Melanoma

With recent interest in immunotherapy on the rise, researchers led by Mirona Attrash treated an older patient presenting with invasive conjunctival melanoma who elected to bypass surgery with the combination of relatlimab-nivolumab (anti-PD-L1/anti-LAG3 inhibitors).

This is the first reported real-world case of a patient successfully treated with relatlimab-nivolumab for conjunctival melanoma, displaying the combination’s high efficacy in treating the complex disease. Up until this point, the combination has been used to treat cutaneous melanoma based on the data from the successful RELATIVITY-047 trial.

RELATIVITY-047

In the global, phase 2-3, double-blind, randomized trial, of the 714 participants with previously untreated unresectable cutaneous melanoma, 359 received single-agent nivolumab and 355 received relatlimab-nivolumab.

The median progression-free survival (PFS) with the combination therapy was 10.1 months (95% CI, 6.4-15.7) versus 4.6 months (95% CI, 3.4-5.6) with nivolumab alone, with a 10.3% difference in the objective response rate.

At 12 months, PFS with relatlimab-nivolumab was 47.7% (95% CI, 41.8-53.2) versus 36% (95% CI, 30.5-41.6) with nivolumab alone.

In terms of safety, grade 3-4 adverse events occurred in 18.9% in the relatlimab-nivolumab group and 9.7% of the nivolumab group.

Rationale for Combination Therapy in Melanoma

The synergistic potential of dual checkpoint inhibition to enhance antitumor immune response was the driving force in the decision to treat this patient and induce rapid response with minimal adverse effects.

The particular success of PD-1/PD-L1 and CTLA-4 inhibitors for the treatment of cutaneous melanoma is what sparked the team’s curiosity to apply the combination to other forms of melanoma.

Real-World Case

In August 2021, an 87-year-old woman with a history of mild dementia presented to a university ophthalmology department with noticeable changes in the anatomy and color of her left conjunctiva.

Invasive conjunctival melanoma was confirmed via biopsy, but because of the patient’s older age and the potential morbidity linked with surgical intervention, the patient decided to bypass surgery.

During the time between her first presentation in 2021 and her first follow-up visit in 2023, the patient did not receive any treatment. She was then admitted in 2023 with a large, exophytic, fungating tumor protruding from her left orbit that obstructed her vision in the left eye. The tumor also caused left eye pain and resultative insomnia.

MRI imaging showed a large, irregular, heterogeneously enhancing mass on the anterior surface of the left eye; the left globe was slightly irregular but overall preserved, with no evidence of posterior orbital extension.

(Left) The patient, before receiving treatment, showed a large, exophytic, fungating tumor protruding from her left orbit, known as a conjunctival melanoma. (Right) Axial MRI T1 weighted with fat suppression showing the tumor. Copyright © 2024 Attrash, Badran, Shapira and Bar-Sela

Comprehensive total body CT showed signs of chronical cerebral vascular incidents, a 2 cm meningioma near the left para-sellar area, slightly enlarged lymph nodes on both sides of the neck, perihilar lymph nodes, and two ground-glass opacity nodules in the right upper lung lobe. No evidence of metastatic disease was detected.

Considering the patient’s tumor size, discomfort levels, and effect on quality of life, the patient’s multidisciplinary team decided to initiate treatment with relatlimab-nivolumab in June 2023.

Treatment Implications and Considerations

Just one month after the patient’s first dose, the tumor remarkably disappeared; the combination therapy demonstrated a dramatic clinical response. However, after the third treatment dose, the patient’s cognitive state significantly worsened, which was treated with prednisone.

(Left) Withdrawal of most of the tumor after receiving one course of relatlimab-nivolumab. (Right) Near complete remission of conjunctival melanoma after receiving the third treatment of relatlimab-nivolumab. Copyright © 2024 Attrash, Badran, Shapira and Bar-Sela

Once the patient discontinued prednisone, she underwent the fourth round of relatlimab-nivolumab treatment. However, due to further worsening of her cognitive state, additional treatment was halted. A tiny residual tumor was still present, but again, it was elected for the patient to not undergo surgery. She could continue living in her home without any further treatment.

Careful benefit-risk considerations must be taken when treating older patients with immunotherapy because of the neurologic side effects that can present with treatment. Although rare, peripheral complications can be fatal. It is not well known whether dementia is a direct side effect of immunotherapy or caused by a regression in a patient’s daily activity due to weakness caused by immune-related adverse events.

Nevertheless, relatlimab-nivolumab treatment for various stubborn melanomas is an avenue that is worth exploring due to the complexity and need for personalization of tumor treatment in the melanoma landscape.

“The case showed this immunotherapy combination’s high efficacy in treating a complex conjunctival melanoma case, sparing primary surgical intervention critical in elderly patients with additional health considerations,” the researchers concluded.