Pathologic complete response to intralesional interleukin-2 therapy associated with improved survival in melanoma patients with in-transit disease.

Abstract

PURPOSE:

Melanoma patients with in-transit disease have a high mortality rate despite various treatment strategies. The aim of this study was to validate the role of intralesional interleukin (IL)-2, to understand its mechanism of action, and to better understand factors that may influence its response.

METHODS:

We retrospectively collected the clinicopathological data of 31 consecutive patients who presented to a tertiary care cancer center for treatment of in-transit melanoma with intralesional IL-2. Kaplan-Meier survival curves and multivariable Cox regression analysis were performed. Immunohistochemistry (IHC) was used to better understand the immune response to localized IL-2 therapy. Targeted next-generation sequencing was performed to genomically characterize the tumors.

RESULTS:

Ten patients (10/31, 32 %) achieved a pathologic complete response (pCR), 17/21 (55 %) had a partial response, and 4/21 (19 %) had progressive disease on treatment. pCR to IL-2 therapy was associated with overall survival (log-rank p = 0.004) and improved progression-free survival (PFS) [adjusted hazard ratio (HR) 0.11; 95 % CI 0.02-0.47; p = 0.003). A higher CD8+ T cell infiltrate was identified in in-transit lesions with a pCR compared with the other lesions (mean IHC score 3.78 vs. 2.61; p = 0.01). Patients with an elevated CD8+ infiltrate demonstrated an improved PFS (unadjusted HR 0.08; 95 % CI 0.01-0.52; p = 0.008).

CONCLUSIONS:

Thirty-two percent of patients achieved pCR with intralesional IL-2 therapy and had a significantly improved PFS compared with the rest of the cohort, which may be explained by a systemic CD8+ T-cell response.

• Authors: Saima Hassan, Teresa M Petrella, Tong Zhang, Suzanne Kamel-Reid, Francesco Nordio, Andrea Baccarelli, Shachar Sade, Karen Naert, Ayman Al Habeeb, Danny Ghazarian, Frances C Wright
• Journal: Annals of surgical oncology (Ann Surg Oncol) Vol. 22 Issue 6 Pg. 1950-8 ( 2015) ISSN: 1534-4681 [Electronic] United States
• PMID: 25366584 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Interleukin-2

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Agents (therapeutic use)
• Female
• Follow-Up Studies
• Humans
• Interleukin-2 (therapeutic use)
• Male
• Melanoma (drug therapy, mortality, pathology)
• Middle Aged
• Neoplasm Staging
• Prognosis
• Prospective Studies
• Retrospective Studies
• Skin Neoplasms (drug therapy, mortality, pathology)
• Survival Rate