| Sumario: | Simple Summary: Cancer immunotherapy using combinations of checkpoint inhibitor antibodies has shown high levels of clinical activity in the treatment of metastatic melanoma. These agents often produce complete remissions of wide-spread melanoma and long-term survival. All current cancer immunotherapy agents have the potential to trigger side effects related to excessive activation of the immune system. While many of these side effects are reversible, immune damage to endocrine organs may unfortunately be permanent. We evaluated how often the relatively new combination of nivolumab plus relatlimab caused problems with endocrine gland function. We found that low thyroid function occurred in about 13.5% of patients, with 11.5% developing low pituitary ("master gland") function. These problems mostly occurred during the period of drug treatment but seemed to persist long-term. The frequency of these changes appeared to occur significantly less frequently than was observed following treatment with an alternative standard regimen consisting of ipilimumab plus nivolumab. Background: Dual immune checkpoint inhibitor therapy with nivolumab plus relatlimab has substantial clinical activity against metastatic melanoma. The incidence and timing of endocrine immune-related adverse events with this treatment remain poorly characterized. Methods: We conducted a retrospective record review of 52 sequential patients who received nivolumab plus relatlimab as initial therapy for metastatic cutaneous melanoma. All patients underwent sequential endocrine screening (TSH, FT4, ACTH, cortisol) prior to each monthly treatment cycle. The incidence and onset of hypothyroidism and hypopituitarism were evaluated, as was cancer treatment outcome. Results: Biochemical evidence for endocrinopathy was identified in 25% of patients. This included a 13.5% incidence of hypothyroidism (median onset 79.0 ± 63.9 days) and 11.5% incidence of hypopituitarism (median onset 243.5 ± 75.6 days). Due to screening and early replacement therapy, there were no related hospitalizations. Patients who developed endocrinopathy showed a trend toward improved progression-free and overall survival. An exploratory analysis suggested that the incidence of endocrinopathy was significantly lower in patients treated with nivolumab plus relatlimab than in those treated with ipilimumab plus nivolumab. Conclusions: During treatment with nivolumab plus relatlimab, endocrinopathy developed in approximately 25% of metastatic melanoma patients, emphasizing a need for screening testing. In an exploratory analysis, endocrinopathy appeared less frequent than in ipilimumab-plus-nivolumab-treated patients. Recovery from endocrinopathy appeared uncommon. Development of delayed endocrinopathy following elective treatment discontinuation for patients in remission was rare (3.8%). Patients who developed endocrinopathy showed a trend toward improved clinical outcome.
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