e22100 Background: Adjuvant pembrolizumab or interferon-alpha has been found to prolong recurrence-free survival as adjuvant therapy for resected melanoma. Several studies have shown that interferon-alpha could modulate immune responses to melanoma. In this study, we provided clear evidence that prior treatment with interferon-alpha significantly enhanced the efficacy of adjuvant pembrolizumab for resected melanoma. Methods: 57 patients with acral or cutaneous melanoma (stage IB or II) were enrolled. After resection of the primary tumors, 25 patients received high-dose interferon-alpha as adjuvant therapy and 32 patients received observation. The patients eventually progressed to stage III or IV, with nodal, in-transit, or resectable distant recurrence. Then the patients underwent complete resection for the recurrent tumors. Next, all the patients were given 100 mg of pembrolizumab every 3 weeks. We compared progression-free survival (the time between the date of starting anti-PD-1 and the date of recurrence after anti-PD-1) between the subgroup receiving prior adjuvant interferon-alpha treatment (IFN-pembrolizumab) and the subgroup receiving observation (pembrolizumab). Results: In the pembrolizumab group, 9.4% (3 of 32) had a recurrence within two months and 38% (12 of 32) had disease progression within four months. Whereas, no patients had a recurrence within two months and the proportion of patients with less than four months PFS was 16% (4 of 25) in the IFN-pembrolizumab group. Furthermore, 44% (11 of 25) had a relapse until the date of last follow-up in the IFN-pembrolizumab group. But 56% (18 of 32) had a recurrence in the pembrolizumab group. The Kaplan-Meier curve showed that PFS was significantly improved in the IFN-pembrolizumab group as compared with the pembrolizumab group (mPFS 34.6 weeks vs. 18 weeks, HR = 0.47, 95% CI 0.23-0.99; p value = 0.0392). For stage III melanoma, mPFS was not reached in the IFN-pembrolizumab group, demonstrating increased benefit for patients with early stage. Altogether, these data suggested that prior interferon-alpha treatment could prolong PFS for adjuvant pembrolizumab. Conclusions: In this study, we for the first time demonstrated that prior treatment with adjuvant IFN-alpha exhibited significant improvement for adjuvant pembrolizumab. Meanwhile, further investigation is required to dissect how IFN-alpha enhanced the efficacy of PD-1 blockade.
Sick sinus syndrome associated with Erdheim-Chester disease was reversed by interferon-alpha treatment
