Intralesional Treatment of Stage III Metastatic Melanoma Patients with L19–IL2 Results in Sustained Clinical and Systemic Immunologic Responses

Abstract

L19-IL2 is a recombinant protein comprising the cytokine IL2 fused to the single-chain monoclonal antibody L19. In previous studies, intralesional injection with IL2 has shown efficacy for the locoregional treatment of cutaneous/subcutaneous metastases in patients with advanced melanoma. The objectives of this study were to investigate whether (i) intralesional delivery of a targeted form of IL2 would yield similar results, with reduction of injection frequency and treatment duration; and (ii) systemic immune responses were induced by the local treatment. Patients with stage IIIB/IIIC melanoma and cutaneous/subcutaneous injectable metastases received weekly intratumoral injections of L19-IL2 at a maximum dose of 10 MIU/week for 4 consecutive weeks. Tumor response was evaluated 12 weeks after the first treatment. Twenty-four of 25 patients were evaluable for therapyinduced responses. A complete response (CR) by modified immune-related response criteria (irRC) of all treated metastases was achieved in 6 patients (25%), with long-lasting responses in most cases (5 patients for !24 months). Objective responses were documented in 53.9% of all index lesions [44.4% CR and 9.5% partial responses (by irRC)], and 36.5% of these remained stable, while 9.5% progressed. Toxicity was comparable with that of free IL2, and no serious adverse events were recorded. A significant temporary increase of peripheral regulatory T cells and natural killer cells, sustained increase of absolute CD4 þ lymphocytes, and decrease of myeloid-derived suppressor cells were observed upon treatment. Finally, we recorded encouraging data about the progression time to distant metastases and overall survival. Cancer Immunol Res; 2(7); 668-78. Ó2014 AACR.

Targeting fibronectin for cancer imaging and therapy

“…L19-IL2 is branded as DARLEUKIN ® for clinical use, and is mainly used to treat melanoma, head and neck cancer, and lymphoma in combination with L19-TNF, dacarbazine or rituximab. Recent phase II clinical evaluation of L19-IL2 in treating melanoma patients showed a promising result in terms of reducing metastasis and extending patient survival 77, 78 . The combined treatment of L19-IL2 and dacarbazine was reasonably tolerated, and all side effects encountered in the study were manageable and reversible.…”

Intratumoral immunotherapy for melanoma

“…Twenty-five patients with stage IIIB/IIIC melanoma and cutaneous/subcutaneous injectable metastases were treated i.t. with L19-IL-2, resulting in complete response (CR) in 25 % of patients by modified immunerelated response criteria (irRC) [96] (Table 1).…”

Armed antibodies for cancer treatment: a promising tool in a changing era

“…Recently, use of the L19-IL2 immunocytokine for the IIT of melanoma patients has been described [41]. Besides an encouraging rate of CR and PR, the results of this trial showed evidence of systemic immune responses, induced by the intralesional treatment.…”

“…Besides an encouraging rate of CR and PR, the results of this trial showed evidence of systemic immune responses, induced by the intralesional treatment. Furthermore, the loco-regional control of in-transit/satellite metastases translated into a slower progression to distant metastases and in an improved overall survival [41].…”