Prior Therapy With Pegylated-Interferon Alfa-2b Improves the Efficacy of Adjuvant Pembrolizumab in Resectable Advanced Melanoma

Abstract

Combination immunotherapy can overcome the limited objective response rates of PD-1 blockade. Interferon alpha (IFN-α) has been proven to be effective in modulating immune responses and may enhance the clinical responses to PD-1 blockade. According to clinical practice guidelines, IFN-α was recommended as adjuvant therapy for stage IIB/C melanoma patients. However, the impact of prior IFN-α therapy on the efficacy of subsequent PD-1 blockade in melanoma has not been previously reported. Therefore, we performed a retrospective analysis for melanoma patients and addressed whether prior IFN-α therapy enhanced adjuvant pembrolizumab as later-line treatment. Fifty-six patients with resectable stage III/IV melanoma who received adjuvant therapy with pembrolizumab were retrospectively enrolled in this study. Notably, 25 patients received adjuvant pegylated IFN-α (PEG-IFN-α) in the prior line of treatment while 31 patients did not receive prior PEG-IFN-α therapy. Cox regression analysis showed that prior PEG-IFN-α therapy was associated with the efficacy of later-line adjuvant pembrolizumab (hazard ratio=0.37, 95% CI 0.16-0.89; P = 0.026). The recurrence rates after treatment with adjuvant pembrolizumab were significantly reduced in the prior PEG-IFN-α group (P < 0.001). The Kaplan-Meier analysis also showed that recurrence-free survival (RFS) after adjuvant pembrolizumab therapy was prolonged by prior PEG-IFN-α treatment (median RFSPem 8.5 months vs. 4.5 months; P = 0.0372). These findings indicated that prior PEG-IFN-α could enhance the efficacy of adjuvant pembrolizumab. The long-lasting effects of PEG-IFN-α provide a new rationale for designing combination or sequential immunotherapy.

Comparison of efficacy and tolerability of adjuvant therapy for resected high-risk stage III-IV cutaneous melanoma: a systemic review and Bayesian network meta-analysis

“…In addition, a retrospective analysis of Jia et al . 65 demonstrated that front-line therapy with IFN may enhance the efficacy of later-line adjuvant therapy with pembrolizumab, which offered the possibility of sequential treatment modalities of IFN and pembrolizumab in resected melanoma.…”

“…64 This combination therapy was also well tolerated, but since Keynote-020 is a single-arm trial, these findings should be interpreted with caution. In addition, a retrospective analysis of Jia et al 65 demonstrated that front-line therapy with IFN may enhance the efficacy of later-line adjuvant therapy with pembrolizumab, which offered the possibility of sequential treatment modalities of IFN and pembrolizumab in resected melanoma.…”

Interferon-Alpha Decreases Cancer Stem Cell Properties and Modulates Exosomes in Malignant Melanoma

“…While IFN-α has been shown to potentially improve recurrence-free survival (RFS) and overall survival (OS) in patients with high-risk melanoma, its effects on OS remain questionable according to some oncologists [28]. Furthermore, adjuvant therapy with PD-1 or BRAF/MEK inhibitors has shown superior results and is being tested in combination with other options such as immunotherapy, further questioning the efficacy of IFN-α as a standalone treatment [29,30]. Despite extensive research, the exact mechanism of IFN-α action in MM remains unclear [3].…”

Medikamentöse Therapie von malignen Lidtumoren

“…Kaliki Ein nachrangiger Ansatz der systemischen Therapie, der hier dennoch zu erwähnen ist, ist der Einsatz von Interferonen. Beispielsweise verbessert eine Vortherapie mit pegyliertem Interferon Alpha-2b das Ansprechen von fortgeschrittenen resektablen Melanomen auf adjuvante Pembrolizumab-Therapie [43]. Außerdem kann Interferon Alpha-2a In Kombination mit 13-cis-Retinsäure der systemischen Therapie von fortgeschrittenen Plattenepithelkarzinomen dienen [44].…”