Incidence and Clinical Impact of Endocrinopathy Following First-Line Nivolumab-Plus-Relatlimab Therapy for Metastatic...

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.

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.

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.

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.