Long-Term Progression-Free Survival of Patients with Metastatic Melanoma or Renal Cell Carcinoma following High-Dose Interleukin-2

Abstract

High-dose interleukin-2 (HD IL-2) was approved in the 1990s after demonstrating durable complete responses (CRs) in some patients with metastatic melanoma (mM) and metastatic renal cell carcinoma (mRCC). Patients who achieve this level of disease control have also demonstrated improved survival compared with patients who progress, but limited data are available describing the long-term course. The aim of this study was to better characterize long-term survival following successful HD IL-2 treatment in patients with no subsequent systemic therapy. Eleven HD IL-2 treatment centers identified patients with survival ≥5 years after HD IL-2, with no subsequent systemic therapy. Survival was evaluated from the date of IL-2 treatment to June 2017. Treatment courses consisted of 2 1-week cycles of HD IL-2. Patients were treated with HD IL-2 alone, or HD IL-2 followed by local therapy to achieve maximal response. 100 patients are reported: 54 patients with mM and 46 patients with mRCC. Progression-free survival (PFS) after HD IL-2 ranges from 5+ years to 30+ years, with a median follow-up of 10+ years. 27 mRCC and 32 mM are alive ≥10 years after IL-2. Thus, a small subset of patients with mM and mRCC achieve long-term PFS (≥5 years) after treatment with HD IL-2 as their only systemic therapy. The ability of HD IL-2 therapy to induce prolonged PFS should be a major consideration in studies of new immunotherapy combinations for mM and mRCC.

Update on the Biology and Management of Renal Cell Carcinoma

“…80 81 In subsequent and contemporary follow-up of patients undergoing this treatment, decadelong disease-free and treatment-free survivors are reported. [82][83][84][85][86][87] A recent report describes the clinical benefit (complete response+partial response+stable disease-CR+PR+SD) and OS for patients treated with IL-2, according to clinical risk groups. 64 For patients treated with IL-2 only, the favorable risk group had a clinical benefit rate of 76% and a median OS of greater than 5 years.…”

“…IL-2 therapy, a T-cell growth factor, is the early immunotherapy which has achieved significant numbers of patients with metastatic RCC having decades-long disease-free survival, possibly cures, following treatment, which is almost unique among advanced adult solid tumors. [82][83][84][85][86][87] These patients include subjects in both favorable and intermediate risk categories and those with clinical benefit after treatment (CR+PR+SD) but particularly CR+PR. 87 Therefore, the goal of all new clinical trials and particularly combination regimens should be to enhance the percentage of patients who achieve durable response and prolonged survival, preferably off-therapy.…”

“…Clinical studies have defined patients with RCC likely to respond to IL-2 as having clear cell histology and excellent performance status 80,81. In subsequent and contemporary follow-up of patients undergoing this treatment, decadelong disease-free and treatment-free survivors are reported 82–87. A recent report describes the clinical benefit (complete response+partial response+stable disease—CR+PR+SD) and OS for patients treated with IL-2, according to clinical risk groups 64.…”

Checkpoint Inhibitors Immunotherapy in Metastatic Melanoma: When to Stop Treatment?

“…There are some previous experiences regarding the discontinuation of immunotherapy in melanoma. Specifically, high-dose interleukin-2 and the anti- CTLA-4 agent ipilimumab were associated with complete and durable responses, albeit limited in number, that occurred within only a few months of therapy [ 35 , 36 ]. However, preliminary data from controlled clinical trials do not point in the same direction.…”

Radiotherapy and High-Dose Interleukin-2: Clinical and Immunological Results of a Proof of Principle Study in Metastatic Melanoma and Renal Cell Carcinoma

“…Early trials of HD IL-2 showed that this treatment elicited durable responses in 10-15% of patients with melanoma and in 15-25% of those with RCC ( 1 – 3 ). Contemporary studies continue to report durable responses and survival rates, mainly in patients obtaining CR ( 38 – 40 ). Encouraged by these recent reports, the interest in IL-2 as a combination or sequential therapy to further improve objective response remains high ( 20 , 41 , 42 ).…”