30th Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2015)
- Poster presentation
- Open Access
- Published:
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
Journal for ImmunoTherapy of Cancer volume 3, Article number: P359 (2015)
Background
HD IL-2 was FDA approved for advanced melanoma, but the data supporting its use dates to the 1990's. The PROCLAIMSM registry (http://www.proclaimregistry.com) is the largest collection of IL-2 treated patients in the US and provides real-time insights into patient survival and 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.
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 (N=236) 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 (IL-2→ipi, n=78), and HD IL-2 followed by PD-1 inhibitors (IL-2→aPD-1, n=35). The majority of patients (22 of 35) in the IL-2→aPD-1 group had progressive disease before receiving subsequent treatment with anti-PD-1/PD-L1-containing regimens. Patients in the HD IL-2 only, IL-2→ipi, and IL-2→aPD-1 groups achieved a mOS of 14, 15.8, and 28.7 months, respectively. The estimated 12-month survival rates were 57%, 64%, and 97%, respectively. There were 10/78 (13%) and 2/35 (5.7%) post therapy treatment-related incidences of autoimmune events in the IL-2→ipi and IL-2→aPD-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 and therapeutically active. These data support the concept of investigating IL-2 therapy in combination or sequence with newly developed immune checkpoint inhibitors.
Author information
Authors and Affiliations
Rights and permissions
Open Access  This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made.
The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.
To view a copy of this licence, visit https://creativecommons.org/licenses/by/4.0/.
The Creative Commons Public Domain Dedication waiver (https://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
About this article
Cite this article
Wong, M.K., Morse, M.A., McDermott, D.F. et al. 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. j. immunotherapy cancer 3 (Suppl 2), P359 (2015). https://doi.org/10.1186/2051-1426-3-S2-P359
Published:
DOI: https://doi.org/10.1186/2051-1426-3-S2-P359
Keywords
- Metastatic Melanoma
- Ipilimumab
- Immune Checkpoint
- Checkpoint Inhibitor
- Advanced Melanoma