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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
  1. Michael KK Wong1,
  2. Michael A Morse2,
  3. David F McDermott3,
  4. Joseph I Clark4,
  5. Howard L Kaufman5,
  6. Gregory A Daniels6,
  7. Jessica C Perritt7,
  8. Hong Hua7 and
  9. Sandra Aung7
  1. Aff1 grid.42505.360000000121566853University of Southern California, Los Angeles Los Angeles CA USA
  2. Aff2 grid.189509.c0000000100241216Duke University Medical Center Durham NC USA
  3. Aff3 grid.239395.70000000090118547The Cytokine Working Group; Division of Hematology/OncologyBeth Israel Deaconess Medical Center Boston MA USA
  4. Aff4 grid.411451.40000000122150876Division of Hematology OncologyLoyola University Medical Center Maywood IL USA
  5. Aff5 Rutgers Cancer Center Institute of New Jersey New Brunswick NJ USA
  6. Aff6 grid.266100.30000000121074242Moores Cancer CenterUniversity of California San Diego La Jolla CA USA
  7. Aff7 grid.437284.ePrometheus Laboratories Inc. San Diego CA USA

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Meeting abstracts


HD IL-2 was FDA approved for advanced melanoma, but the data supporting its use dates to the 1990's. The PROCLAIMSM registry ( 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.


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.


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.


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.