Abstract
BACKGROUND The combination of anti-CTLA4 and anti-PD-1 immune checkpoint inhibitors (ICIs) has replaced chemotherapy as the most effective first-line therapy for advanced-stage melanoma, associated with a median overall survival of 72 months. Irrespective of BRAF status, ipilimumab-nivolumab (IPINIVO) is the most effective first-line approach but treatment-limiting toxicities are twice as common as with other ICIs. In recurrent disease, rechallenging with the same dual therapy has not shown great efficacy, although rechallenge with ipilimumab (anti-CTLA-4) is not well studied. Reported studies were limited by small sample sizes and populations with recurrence <24 months after initial therapy. CASE REPORT We present a 40-year-old woman with a history of resected stage IIIc, BRAF wild-type melanoma, previously treated in the adjuvant setting with low-dose IPINIVO (1: 3 mg/kg ipilimumab: nivolumab), with systemic progression in the peritoneum 7 years later, showing nodularity and ulceration at the original site with progressive abdominal and pelvic pressure. The patient was rechallenged with standard-dose IPINIVO (3: 1 mg/kg iplimumab: nivolumab) and achieved excellent clinical response despite multiple treatment-delaying toxicities: grade 2 cytokine release syndrome after cycle 1 and grade 2 pneumonitis and grade 3 colitis after cycle 2, managed with high-dose prednisone. The patient remains on maintenance nivolumab with ongoing radiographic and clinical response for over 18 months. CONCLUSIONS There are limited data on the benefit and safety of IPINIVO with rechallenge in patients who achieved initial PFS longer than 2 years, warranting further research in populations with resistant disease. Long-term safety data from rechallenge responders are needed.