Background: The PROCLAIMSM registry (, created in 2011, is the largest collection of IL-2 treated patients in the US and provides real-time insights into sequencing or combining IL-2 with new and old therapies and how this may affect patient outcomes. Previously, we reported a median overall survival (mOS) of 20 months with a median follow-up of 37 months in metastatic melanoma (mM) patients treated with high dose IL-2 (HD IL-2) between 2007 and 2012 from a retrospective cohort. These findings led to the hypothesis that improved mOS may have been a result of subsequent salvage therapies, including checkpoint inhibitors.

Purpose: To report on the analysis of survival data from 26 sites.

Methods: Patients must have received at least one dose of HD IL-2 for this analysis. Those that received checkpoint therapy prior to HD IL-2 were excluded. Statistics and survival analysis on prospectively entered patients were performed on datasets as of March 16th, 2015.

Results: The median overall survival (mOS) for the 236 patients was 18.4 months with a median follow-up of 21.7 months. Patients were stratified into three groups; HD IL-2 only (n=123), HD IL-2 followed by ipilimumab (Post ipi, n=78), and HD IL-2 followed by PD-1 inhibitors (Post αPD-1, n=35). There were four patients in the Post αPD-1 group that received anti-PD-L1 treatment. Patients in the HD IL-2 only, Post ipi, and Post αPD-1 groups achieved a mOS of 14, 15.7, and 28.7 months, respectively. The estimated 12-month survival rates were 56%, 64%, and 97%, respectively. There were 10/78 (13%) and 3/35 (8.6%) post therapy treatment-related incidences of autoimmune events in the Post Ipi and Post αPD-1 groups, respectively. No treatment related deaths were reported.

Conclusions: This is the first report of clinical data relating to HD IL-2 use followed by checkpoint blockade of the PD-1 pathway. Treatment with anti-PD-1 after initial therapy with HD IL-2 had significantly prolonged survival compared to patients treated with ipilimumab. Moreover, improved survival was not observed in patients treated with follow-on ipilimumab compared to patients treated only with HD IL-2. Anti-PD-1 therapy after HD IL-2, appears to be safe, is therapeutically active. These data support the concept of investigating IL-2 therapy in combination or sequence with newly developed immune checkpoint inhibitors.

Citation Format: Michael K.K. Wong, Michael A. Morse, David F. McDermott, Joseph I. Clark, Howard L. Kaufman, Gregory A. Daniels, Hong Hua, Sandra Aung. Overall survival of metastatic melanoma patients treated with HD IL-2 followed by immune checkpoint blockade of the CTLA-4 or the PD-1 pathways: Analysis of data on the current use of HD IL-2. [abstract]. In: Proceedings of the CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference: Translating Science into Survival; September 16-19, 2015; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(1 Suppl):Abstract nr B140.