title: Clinical characteristics and treatment-related biomarkers associated with response to high-dose interleukin-2 in metastatic melanoma and renal cell carcinoma: retrospective analysis of an academic community hospital's experience.
abstract: BACKGROUND
  Immunotherapy in the treatment of metastatic melanoma and renal cell carcinoma can produce durable therapeutic responses, which may improve survival. We aimed to identify clinical characteristics and biomarkers associated with response to high-dose interleukin-2 therapy (IL-2) in patients with metastatic melanoma and renal cell carcinoma treated at an academic community hospital.
  
  
  METHODS
  We retrospectively analyzed clinical variables and biomarkers of 50 consecutive metastatic melanoma or renal cell carcinoma patients treated at our institution with IL-2 during 2004 - 2012. We evaluated clinical characteristics: metastatic sites of disease, prior therapies, number of IL-2 doses per cycle, response duration, autoimmune phenomena, and peak fever, as well as laboratory biomarkers: baseline LDH, platelet nadir, and baseline and highest absolute lymphocyte count (ALC). Survival outcomes were calculated using Kaplan-Meier curves.
  
  
  RESULTS
  Variables differing between responders (clinical benefit group) and non-responders (no clinical benefit group) in metastatic melanoma included platelet nadir during treatment (p = 0.015), autoimmune phenomena (p = 0.049), and in renal cell carcinoma, platelet nadir (p = 0.026). There were no significant differences between number of doses of IL-2 received per cycle and response in either cancer subtype. Clinical benefit occurred in 25% of patients (9/36) when IL-2 was given as first-line therapy. Median overall survival for the clinical benefit group from the initiation of IL-2 to death or last follow-up was 61 months versus 17 months for the no clinical benefit group (p < 0.001) for metastatic melanoma. In renal cell carcinoma overall survival for clinical benefit patients was 48 months versus 17 months. No treatment-related deaths occurred.
  
  
  CONCLUSIONS
  High-dose IL-2 can be safely administered by an experienced team in a non-intensive care oncology unit. The clinical benefit group developed autoimmune phenomena (melanoma patients), lower platelet nadir, and on average, received the same number of IL-2 doses as the no clinical benefit group, suggesting a response relationship to the patient's baseline immune status. Further investigation of immune predictors of response may be useful to select appropriate patients for this therapy.
authors: Department of Hematology Oncology, Lehigh Valley Health Network, John and Dorothy Morgan Cancer Center, 1240 S Cedar Crest Blvd, Suite 401, Allentown, PA 18103 USA.
authors: Christine
authors: C
authors: Saraceni
authors: Department of Hematology Oncology, Lehigh Valley Health Network, John and Dorothy Morgan Cancer Center, 1240 S Cedar Crest Blvd, Suite 401, Allentown, PA 18103 USA.
authors: Nicole
authors: N
authors: Agostino
authors: Lehigh Valley Health Network, Health Systems Research and Innovation, 1628 Chew Street, 3rd Floor, Allentown, PA 18102 USA.
authors: Michael J
authors: MJ
authors: Weiss
authors: Department of Hematology Oncology, Lehigh Valley Health Network, John and Dorothy Morgan Cancer Center, 1240 S Cedar Crest Blvd, Suite 401, Allentown, PA 18103 USA.
authors: Katherine
authors: K
authors: Harris
authors: Department of Hematology Oncology, Lehigh Valley Health Network, John and Dorothy Morgan Cancer Center, 1240 S Cedar Crest Blvd, Suite 401, Allentown, PA 18103 USA.
authors: Suresh
authors: S
authors: Nair
keywords: Biomarkers; IL-2; Interleukin-2; Metastatic melanoma; Metastatic renal cell carcinoma; Response; Safety