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

BackgroundImmunotherapy 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.Patients/MethodsWe 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.ResultsVariables 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.ConclusionsHigh-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.

Development of thyroid dysfunction is associated with clinical response to PD-1 blockade treatment in patients with advanced non-small cell lung cancer

“…A meta-analysis of skin rash and outcomes of NSCLC with EGFR-TKIs treatment found a significant association between skin rash and favorable outcomes. 11 In IL-2 treatment of metastatic melanoma, many studies 12,13 have shown that immunologic side effects such as vitiligo and thyroiditis correlate with good clinical response to IL-2 therapy. Furthermore, a meta-analysis of immune checkpoint inhibitor therapy in melanoma found that vitiligo (skin irAE) was significantly associated with both longer PFS and OS, 20 although thyroiditis was not in another study.…”

“…It is noteworthy that thyroiditis, which is one of the most common immune-related adverse event (irAE), is associated with the mechanism of the antitumor effect of immunotherapy, and can be easily monitored with a thyroid function test (TFT) in a clinical setting. [8][9][10] In patients treated with several other drugs, side effects related to drug mechanisms such as skin rash after epidermal growth factor receptor tyrosine kinase inhibitor use (EGFR-TKIs) 11 or vitiligo and thyroiditis after IL-2 treatment 12,13 are associated with a good prognosis. Interestingly, Dr. Osorio et al recently reported that thyroid dysfunction after pembrolizumab in NSCLC patients was associated with longer OS in an unadjusted analysis.…”