L19-IL2 is a single-chain monoclonal antibody comprising the recombinant protein of cytokine IL2 fused to L19. In previous studies, intralesional injection with IL2 had shown efficacy for the loco-regional treatment of cutaneous/subcutaneous metastases in advanced melanoma patients. Objectives of the current study were to investigate whether: (a) intralesional delivery of a targeted form of IL2 would yield similar results, with reduction of injection frequency and treatment duration; and (b) 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 twelve weeks after the first treatment. Twenty-four of 25 patients were evaluable for therapy-induced responses. A complete response (irCR) by 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 (OR) were documented in 53.9% of all index lesions (44.4% irCR and 9.5% partial responses (irPR) by irRC), 36.5% of these remained stable, while 9.5% progressed. Toxicity was comparable to that of free IL2, no serious adverse events were recorded. A significant temporary increase of peripheral regulatory T cells and natural killer cells, sustained increase of absolute CD4+ lymphocytes, and decrease of myeloid-derived suppressor cells were observed upon treatment. Finally, we recorded encouraging data regarding the progression time to distant metastases and overall survival. -
- Received November 22, 2013.
- Revision received March 18, 2014.
- Accepted March 18, 2014.
- Copyright © 2014, American Association for Cancer Research.