Real-world efficacy of nivolumab in Peruvian patients with advanced melanoma.
Authors: Roque Katia , Valencia Guillermo , Rioja Patricia , huaman Campos jose Andres , Colomo Costas Valeria , Mantilla Raul , Morante Zaida , Fuentes Hugo , Munante Bruno , Vidaurre Tatiana , Neciosup Silvia P. , De Mello Ramon Andrade B , Gomez Henry Leonidas , Castaneda Altamirano Carlos Arturo 
Published: June 2023

e18849

Background: Malignant melanoma in Latin American (LATAM) population has aggressive features as higher rates of Acral lentiginous (ALM) subtype and shorter survival. Immunotherapy has improved prognosis among patients with cutaneous melanoma; however, there is scarce reports of the effectiveness in LATAM population. We describe our experience with management and survival of Peruvian patients with advanced melanoma treated whit nivolumab. Methods: A retrospective study based on cases review evaluated the efficacy of nivolumab. Eligible patients were metastatic, recurrent or unresectable malignant melanoma undergoing treatment with nivolumab as first-line for at least 3 consecutive months between 2020 and February 2021 in two institutions (Instituto Nacional de Enfermedades Neoplasicas, Oncosalud). Clinical pathologic features and immune inflammatory blood markers (neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and prognostic nutritional index (PNI)) were evaluated. Efficacy was measured as progression-free survival (PFS), objective response rate (ORR), Clinical benefit rate (CBR) and overall survival (OS). A p < 0.05 value (SPSS) will be considered for a significant difference. Results: 57 patients were analyzed; median age was 63 yo (range 34-83); 59.6% were female. 77.2% had a Zubrod 0-1. Regarding histology, 37% (n = 21) had acral subtype, 38% (n = 22) non-acral, 17% (n = 10) mucosal and 8% (n = 4) unknown primary (UP). 81.1% had negative BRAF mutation status, and the median lactate dehydrogenase (LDH) level was 257 U/L (130-1281). 63.2% had visceral metastasis, the most common site being lung (42%) and liver (9%). Central nervous system (CNS) metastases was reported in 5%. After a median follow-up was 25 months, the median OS reported was 51.43 months (95% CI, 14.23-88.62). Median OS was 28.93 for acral melanoma (95% CI, 14.66-43.19) and not reached for other subtypes. Median PFS was 7.93 months (95% CI, 2.49-13.36); 4.93, 14.73 and 5.26 months in patients with acral, non-acral and mucosal melanoma, respectively. A significant difference was founded in OS (p = 0.024) and PFS (p = 0.001) between acral and non-acral melanoma. ORR was reached in 28.1% of patients; 19%, 31.8% and 20% in acral, non-acral and mucosal subtype, respectively. However, global CBR was 64.9%, with the higher and lower rate for non-acral (81.82%) and mucosal melanoma (50%). The overall incidence of immune related adverse effects (irAEs) was 69.5%, the most common were skin reactions (14%), followed by asthenia (12%); not grade 3-4 AEs were reported. Regarding immune inflammatory blood markers, no association between PFS with NLR (p = 0.49), PLR (p = 0.3) and PNI (p = 0.71) were founded. Conclusions: Nivolumab showed efficacy in improving OS for patients with advanced melanoma, however ALM had shorter OS and PFS. No prognostic immune blood markers were reported. New biomarkers are necessary, especially in acral melanoma.