The Role of Interleukin in the Treatment of Malignant Melanoma and Renal Cell Carcinoma
High dose interleukin-2 (HD IL-2), has been in clinical use in the treatment of metastatic renal cell carcinoma (mRCC) and metastatic melanoma (mM) for over 20 years, and has elicited durable responses in selected patients, resulting in cures in some cases without chronic toxicity or the need for further therapy. However, in the era of targeted therapies such as tyrosine kinase inhibitors (TKIs) and emerging use of immune checkpoint inhibitors such as anti-programmed cell death-1 (PD-1) agents, the role of HD IL-2 has become unclear.
At ASCO 2016, Professor Ajjai Alva of the University of Michigan outlined how HD IL-2 fit into current treatment paradigms. HD-IL-2 is the only US Food and Drug Administration (FDA)-approved therapy that provides long-term remission. Currently, data is being presented at ASCO on new immunotherapies; how IL-2 will fit in with those therapies as well as TKIs remains to be seen. Nevertheless, IL-2 produces a durable response in a subset of patients in mRCC and mM, and therefore will continue to play a role in treatment. It is also noteworthy that a significant proportion of patients receiving HD IL-2 achieve stable disease, a clinically beneficial event that is associated with prolonged overall survival.
Traditionally, HD IL-2 was used only in treatment naive patients because it was the first approved treatment for mRCC. However, an increasing number of patients are receiving TKIs as initial treatment before undergoing HD IL-2 treatment. Published data show that HD IL-2 is safe and effective after prior TKI therapy.1 While the optimum sequence of these agents remains uncertain, it seems likely that HD IL-2 will be employed at an early treatment stage.
Dr Howard Kaufman of the Rutgers Cancer Institute of New Jersey discussed the PROCLAIM (Proleukin Observational Registry to Evaluate the Treatment Patterns and Clinical Response in Malignancy) registry, which collects information on patients treated with HD IL-2. The registry aims to help us understand the factors associated with good outcomes in IL-2 and how IL-2 will fit into the treatment landscape. PROCLAIM started with a retrospective cohort and then began prospectively collecting patient data.
The key findings of PROCLAIM to date show that the response rates reported around a decade ago are still intact. The overall response rate is similar to that reported in initial studies, around 17%. In addition, in this large cohort of patients, a manageable toxicity profile has been reported. Recent data from the PROCLAIM registry suggests that patients with previous exposure to HD IL-2 have a higher response to anti-PD1 therapies. These findings have generated important hypotheses that may be explored in future clinical studies.
A predictive biomarker would represent a significant advance. Early data suggested that pretreatment levels of serum VEGF and fibronectin were independent predictors of response to Il-2.2 The Select trial aimed to prospectively validate these findings as well as investigating other markers. The study is now complete and results are awaited.
Disclosures: Katrina Mountfort is an employee of Touch Medical Media. The publication of this article was supported by Prometheus.
1. Lam ET, Wong MK, Agarwal N, et al., Retrospective analysis of the safety and efficacy of high-dose interleukin-2 after prior tyrosine kinase inhibitor therapy in patients with advanced renal cell carcinoma, J Immunother, 2014;37:360-5.
2. Sabatino M, Kim-Schulze S, Panelli MC, et al., Serum vascular endothelial growth factor and fibronectin predict clinical response to high-dose interleukin-2 therapy, J Clin Oncol, 2009;27:2645-52.