High response rate after intratumoral treatment with interleukin‐2

Abstract

BACKGROUND: Systemic high-dose interleukin-2 (IL-2) achieved long-term survival in a subset of patients with advanced melanoma. The authors reported previously that intratumorally applied IL-2 induced complete local responses of all metastases in >60% of patients. The objectives of the current study were to confirm those results in a larger cohort and to identify patient or regimen characteristics associated with response. METHODS: Patients with melanoma who had a median of 12 injectable metastases received intratumoral IL-2 treatments 3 times weekly until they achieved clinical remission. The initial dose of 3 million international units was escalated, depending on the individual patient's tolerance. RESULTS: Forty-eight of 51 patients were evaluable. Only grade 1/2 toxicity was recorded. A complete response that lasted 6 months was documented in 70% of all injected metastases. A complete local response of all treated metastases was achieved in 33 patients (69%), including 11 patients who had between 20 and 100 metastases. Response rates were higher for patients who had stage III disease compared with patients who had stage IV disease. No objective responses of distant untreated metastases were observed. The 2-year survival rate was 77% for patients with stage IIIB/IIIC disease and 53% for patients with stage IV disease. Efficacy and survival did not differ between patients who had 20 lesions and patients who had <20 lesions. CONCLUSIONS: Intratumoral IL-2 treatment elicited complete local responses in a high percentage of patients. Further studies will be required to investigate the mode of action of this treatment and its impact on survival. Cancer 2010;116:4139-46.

Oncolytic Adenoviruses Armed with Tumor Necrosis Factor Alpha and Interleukin-2 Enable Successful Adoptive Cell Therapy

“…Regarding prior knowledge about the recombinant proteins, IL-2 has been widely used in treating malignant melanoma and renal cell carcinoma 18 and it stimulates T cell proliferation and differentiation 9, 19, 20. Like IL-2, TNF-α can activate immune cells, 21 but it also induces antitumor inflammation and the production of other cytokines and chemokines 22, 23.…”

Developments in Intralesional Therapy for Metastatic Melanoma

“…12,13,18,23,36,37 The number of study patients in published reports has been small: 7 participants treated in 1 documented case series and 23, 39, and 48 study patients in 3 phase 2 studies. 18,39,58,59 Response rates consistently exceed 80%. 36,58,59 …”

“…9 Evidence suggests that subcutaneous lesions are less responsive than cutaneous lesions, and tumors with smaller bulk are more likely to regress under treatment. 16–18 Investigators have attempted to limit intralesional volumes to 1 mL or less to minimize the local adverse events that result from injecting higher volumes. 16 …”

Immunotherapy of Melanoma

“…IL-2 has been shown to deliver long-lasting remission in this patient subgroup. Intralesional IL-2 led to response rates of up to 80% [16,17]. The rate of durable complete remissions (CRs) in treated metastases was also remarkable: 70% of the treated patients remained in CR for more than 6 months [17].…”