Neoadjuvant Pembrolizumab and High Dose Interferon Alfa-2b in Resectable Regionally Advanced Melanoma
Mené sur 31 patients atteints d'un mélanome de stade localement avancé et résécable, cet essai évalue l'efficacité, du point de vue du taux de réponse globale, de la réponse pathologique complète, de la survie sans récidive et de la survie globale, et la toxicité du pembrolizumab combiné à de hautes doses d'interféron alpha-2b en traitement néoadjuvant
Purpose: Neoadjuvant immunotherapy may improve the clinical outcome of regionally advanced operable melanoma and allows for rapid clinical and pathologic assessment of response. We examined neoadjuvant pembrolizumab and high dose interferon alfa-2b (HDI) therapy in patients with resectable advanced melanoma. Patients and Methods : Patients with resectable stage III/IV melanoma were treated with concurrent pembrolizumab 200 mg intravenously (IV) every 3 weeks and HDI 20 MU/m2/day IV, 5 days/week for 4 weeks, then 10 MU/m2/day subcutaneously 3 days/week for 2 weeks. Definitive surgery followed, and adjuvant combination immunotherapy completing a year of treatment. Primary endpoint was safety of the combination. Secondary endpoints included overall response rate (ORR), pathologic complete response (pCR), recurrence-free survival (RFS), and overall survival (OS). Blood samples for correlative studies were collected throughout. Tumor tissue was assessed by immunohistochemistry (IHC) and flow cytometry at baseline and at surgery. Results : 31 patients were enrolled, and 30 were evaluable. At data cutoff (October 2, 2019), median follow-up for OS was 37.87 months (range; 33.2-43.47). Median OS and RFS were not reached. Radiographic ORR was 73.3% (95% CI: 55.5%-85.8%), with a 43% (95% CI: 27.3%-60.1%) pathologic complete response (pCR) rate. None of the patients with a pCR have recurred. HDI and pembrolizumab were discontinued in 73% and 43% of patients, respectively. Correlative analyses suggested that intratumoral PD-1/PD-L1 interaction and HLA-DR expression are associated with pCR (p=0.002 and p=0.008, respectively). Conclusions : Neoadjuvant concurrent HDI and pembrolizumab demonstrated promising clinical activity despite high rates of treatment discontinuation. pCR is a prognostic indicator.