Limited efficacy of intratumoral IL-2 applied to large melanoma metastases.

Abstract

We recommended increased doses of 6 MIU per individual lesions larger than 2 cm [3, 4]. IL-2 has different known dose dependent, in part opposite effects, like expansion of regulatory T cells and induction of their suppressive characteristics or on the other hand activation of cellular antitumor immunity [5]. Therefore, we assume that a high concentration of IL-2 at a tumor tissue is crucial for efficacy. These high concentrations can only insufficiently be reached through systemic therapy, with its dose-limiting toxicity [6] or by low doses of IL-2 injected in large metastases. Therefore and in contrast to our initial recommendations, we currently restrict intratumoral therapy with free IL-2 to lesions up to 1 cm in longest diameter and increase the dose per lesion as tolerated up to a maximum of 18 MIU units IL-2 per day. Recurrences developing during therapy should be included in subsequent treatments as soon as these become evident. In contrast, the applied dose in the patient presented by Moreno-Ramirez et al. with 6–10 MIU IL-2 applied on two bulky lesions, each with ~5 cm diameter, seems low. Recently, the use of an antibody-based targeted version of IL-2 has exhibited promising anticancer effects in patients with stage IIIC melanoma. The use of the L19–IL2 fusion protein has allowed us to reduce the number of injections and is accompanied by favorable time-to-stage IV profiles [2]. Using this dataset, we now analyzed the rate of complete responses according to longest diameter of the lesion (Table 1). Promising complete responses were likewise observed in lesions larger than 1 cm, but due to the low number of large lesions in this trial, it is not clear whether the targeted form of IL-2 offers an advantage over free IL-2 for treatment of larger lesions. If patients present several metastases of different diameters at baseline, a combined strategy, including initial Dear Editors,