28 | Efficacy and toxicity outcomes with doublet immunotherapy in metastatic melanoma: the real-world REALIPINIVO study

Miriam Forte¹, Francesco Caraglia¹, Silvana Cozzolino¹, Antonino Colloca¹, Alfonso Esposito¹, Maria Cristina Giugliano¹, Eleonora Cioli¹, Marcella Scala², Francesca Sparano⁵, Maria Chiara Sergi³, Teresa Del Giudice⁴, Immacolata Paciolla⁶, Luigi Formisano², Stefania Napolitano¹, Antonio Maria Grimaldi⁶, Paolo Antonio Ascierto⁵, Fortunato Ciardiello¹, Teresa Troiani¹, Vincenzo De Falco¹ | ¹Medical Oncology, Department of Precision Medicine, Università degli Studi della Campania Luigi Vanvitelli, Naples; ²Department of Clinical Medicine and Surgery, Federico Il University, Naples; ³Unità Operativa Complessa di Oncologia Medica, Ospedale "Mons. A.R. Dimiccoli", Barletta; ⁴Nuclear Medicine Unit, "Mater Domini" University Hospital, Catanzaro; ⁵Istituto Nazionale Tumori IRCCS Fondazione Giovanni Pascale Melanoma, Cancer Immunotherapy and Development Therapeutics Unit, Napoli; ⁶Medical Oncology Unit AORN "San Pio", Benevento, Italy.

Background: Immunotherapy has significantly improved survival outcomes in metastatic melanoma. Following the Checkmate 067, in January 2022, the Italian Medicines Agency (AIFA) approved combination of Nivolumab+Ipilimumab for the treatment of metastatic melanoma in adults with asymptomatic brain metastases or with PD-L1 < 1%.

Methods: This retrospective observational study, conducted across Gruppo Oncologico dell'Italia Meridionale (GOIM) centers, evaluated safety and efficacy of Nivolumab + Ipilimumab in real-world conditions.

Results: The study involved 6 centers in southern Italy and 72 patients treated with Nivolumab + Ipilimumab from January 2022 to January 2025. The majority of patients (63,9%) were male with median age of 56.8 years, All of them had a stage IV melanoma diagnosis, of which 40.3% had brain metastasis, 63.9% of patients had BRAF V600 mutation and 79.2% had PD-L 1 <1%. About 62.5% were naïve from systemic treatment, 24% had been subjected to adjuvant therapy (targeted or immunotherapy), while 10.4% had carried out first line with targeted therapy. Overall response rate was 54.2% (complete response were 25%) while 18% had progressive disease as best response. With a median follow-up of 13.6 months, median PFS was 17,03 months (95% CI 4,8 -18,6), median OS was not reached. Regarding safety, 72% of patients experienced an adverse event of any grade,58,3% were grade 3-4. The most frequent adverse events were diarrhea (37.5%), hypertransaminasemia (30.5%), skin toxicity (25%), thyroiditis (19.4%). Severe side effects led to hospitalization in 30.6% of patients (Table 1). Molecular analyses on patients' tissue samples are ongoing to investigate correlations between molecular features and outcomes (Cox regression showed an association with survival only with objective response and the number of metastatic sites).

Conclusions: This study confirmed efficacy of immunotherapy doublet in a real-world context. Safety data were better than in the registration studies, perhaps due to greater experience in managing side effects.

---

Table 1.