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Editorial Immunotherapy Cancer Immunotherapy with Interleukin-2— The PROCLAIM SM Registry Howard L Kaufman Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey, US H igh dose interleukin (HD IL-2) is an approved therapy for the treatment of metastatic renal cell carcinoma (mRCC) and metastatic melanoma (mM) that is capable of inducing durable complete responses. The role and clinical value of HD IL-2 needs to be re-examined and better delineated in this era of emerging targeted therapy and immune checkpoint blockade therapies. This editorial presents a perspective based on recent experience using PROCLAIM SM , a large multicenter retrospective and prospective registry of patients receiving HD IL-2. The data reported confirms the potential for durable survival as first reported for HD IL-2 over two decades ago, and supports further investigation of IL-2 therapy in combination or sequence with immune checkpoint inhibitors. Keywords Immunotherapy, interleukin-2, metastatic melanoma, metastatic renal cell carcinoma Disclosure: Howard L Kaufman has served on advisory boards for Prometheus. This article is a short opinion piece and has not been submitted to external peer reviewers, but was reviewed by the Editorial Board before publication. Acknowledgments: Medical writing support was provided by Katrina Mountfort, of Touch Medical Media and funded by Prometheus. Authorship: All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship of this manuscript, take responsibility for the integrity of the work as a whole, and have given final approval to the version to be published. Open Access: This article is published under the Creative Commons Attribution Noncommercial License, which permits any noncommercial use, distribution, adaptation, and reproduction provided the original author(s) and source are given appropriate credit. Received: September 5, 2016 Published Online: November 2, 2016 Citation: Oncology & Hematology Review, 2016;12(2):77–9 Corresponding Author: Howard L Kaufman, Rutgers Cancer Institute of New Jersey, 145 Little Albany St, New Brunswick, New Jersey, US. E: Support: The publication of this article was supported by Prometheus. The views and opinions expressed are those of the author and do not necessarily reflect those of Prometheus. Metastatic melanoma (mM) and metastatic renal cell carcinoma (mRCC) are potentially lethal cancers with overall poor prognosis. High dose interleukin-2 (HD IL-2; Proleukin ® , Prometheus Laboratories Inc, San Diego, California) was approved by the US Food and Drug Administration (FDA) in 1992 for the treatment of mRCC and in 1998 for the treatment of mM. Approval was based on data from a number of clinical trials demonstrating consistent objective responses, including complete responses (CR) in select patients. 1 These responses have proven to be durable for decades. However, the use of HD IL-2 is associated with manageable short-term toxicity and requires hospitalization, utilizing the intervention of specialist teams experienced in HD IL-2 therapy. 2 In addition, only a minority (16% in mM and 15% in mRCC) of patients respond to treatment, based on the initial data reported in the package insert. 1 The emergence of immune checkpoint inhibitors such as the anti-programmed cell death 1 (PD-1) and programmed death-ligand 1 (PDL-1) agents provides a potentially more convenient immunotherapy option. However, durable efficacy data are still pending for PD-1 targeted regimens. Recent reports confirm that incorporating HD IL-2 into treatment strategies for mRCC can induce CR: in a National Cancer database study (n=91), four patients (4.5%) had a CR, 10 (11.4%) had a partial response, and 28 (31.8%) had a stable disease. 3 A retrospective study of patients with mRCC (n=186) and melanoma (n=314) treated with HD IL-2 between 1997 and 2012 reported complete and partial responses in 12% and 16% of patients with melanoma and 7% and 17% of patients with mRCC, respectively. 4 Since overall survival (OS) in patients treated with HD IL-2 may extend to decades, registry studies are useful for assessing long-term response, as well as for generating hypotheses to guide future clinical directions. This editorial will discuss the continued role of HD IL-2 within current therapeutic paradigms, as well as discussing the implications of the PROCLAIM SM (Proleukin Observational Registry to Evaluate the Treatment Patterns and Clinical Response in Malignancy) registry on current clinical practice. The role of HD IL-2 within current therapeutic paradigms HD IL-2 is an FDA-approved therapy known to produce long-term remissions in mRCC and mM. HD IL-2 was the first approved treatment for mRCC. HD IL-2 outcomes have been better in patients with a good performance status, and and hence it was traditionally used as first line treatment. However, an increasing number of mRCC patients are receiving tyrosine kinase inhibitors (TKIs) or immune checkpoint inhibitors as initial treatment before undergoing HD IL-2 treatment. A retrospective study of 40 consecutive mRCC patients, who were treated with HD IL-2 after at least one prior TKI therapy, concluded that that HD IL-2 was effective and with a manageable toxicity profile in patients who had received prior TKI therapy. 5 In melanoma, patients with BRAF mutations in their tumors may receive BRAF/MEK targeted therapy and those with wild-type BRAF status may receive immune checkpoint directed therapy prior to considering HD IL-2. 6 The clinical benefit of using HD IL-2 and TOU CH MED ICA L MEDIA 77