The prognostic significance of stable disease following high-dose interleukin-2 (IL-2) treatment in patients with metastatic melanoma and renal cell carcinoma

Abstract

High-dose interleukin-2 (HD IL-2) is an approved immunotherapy agent for metastatic melanoma and renal cell carcinoma resulting in objective responses in 15-20 % of patients. An additional subset of patients achieves stable disease, and the natural history of these patients has not been well documented. We hypothesized that stable disease following HD IL-2 is associated with a survival advantage. To explore this hypothesis, a retrospective chart review of 305 patients diagnosed with metastatic melanoma or renal cell carcinoma treated with HD IL-2 was conducted. Patient characteristics, response based on standard RECIST criteria and overall survival were analyzed using the Kaplan-Meier method and associations with clinical response were compared using a log-rank test. Two hundred and forty-five patients had melanoma and 60 had renal cell carcinoma. Of these, 217 had complete data available for analysis. Fifty-nine percentage had progressive disease (PD), 26 % had stable disease (SD) and 15 % had an objective complete (CR) or partial response (PR). Median overall survival was 16.8 months for all patients with available survival data; patients with PD had a median survival of 7.9 months compared to 38.2 months for stable disease, while the median has not been reached for those with objective responses. This retrospective data support an association between overall survival and stable disease, suggesting that clinical benefit may be underestimated for patients treated with HD IL-2. The data further support the use of disease control rate (CR + PR + SD) as a more meaningful endpoint for future clinical studies of tumor immunotherapy, including future studies of HD IL-2.

Fig. 1

Consort diagram showing 305 total patients had received treatment in the defined study period. Of these, 217 patients had both response and survival data available and are included in the final survival analysis depicted in Figs. 2b–4

Fig. 2

Overall survival of patients treated with high-dose IL-2. a Kaplan–Meier analysis of overall survival of all patients (n = 226) treated with HD IL-2 was 16.8 months for whom survival data were available Note: Not all patients had response data available, and these subjects are excluded from subsequent analyses; b Traditional Kaplan–Meier analysis of overall survival based on RECIST response to one course of IL-2 treatment. Objective responders (blue line) do not reach a median survival, whereas the median survival among those without an objective response (green line) is 13.9 months (Log-rank test; p = 0.001)

Fig. 3

Patients with stable disease following high-dose IL-2 have improved survival compared to non-responders. Patients with stable disease (green) have a median survival of 38.2 months, compared to just 7.2 months among patients with progressive disease (purple; p = 0.001). Patients with an objective response (blue) have even better survival with no median reached (p = 0.001)

Fig. 4

The disease control rate (DCR) is associated with improved overall survival in patients receiving high-dose IL-2. Patients with disease control (CR + PR + SD; blue line) have a median survival of 50.4 months compared to 7.2 months among patients with progressive disease (green line; p = 0.001)