High dose interleukin-2 (Aldesleukin) - expert consensus on best management practices-2014

Abstract

Interleukin-2 (IL-2) was historically one of the few treatments for adults with stage IV solid tumors that could produce complete responses (CRs) that were often durable for decades without further therapy. The majority of complete responders with metastatic renal cell carcinoma (mRCC) and metastatic melanoma (mM) could probably be classified as "cures". Recent publications have suggested improved efficacy, perhaps due to improved patient selection based on a better understanding of clinical features predicting outcomes. Guidelines for clinical management were established from experience at the National Cancer Institute (NCI) and an affiliation of institutions known as the Cytokine Working Group (CWG), who were among the first to utilize HD IL-2 treatment outside of the NCI. As new centers have opened, further management variations have emerged based upon center-specific experience, to optimize administration of IL-2 and provide high quality care for patients at each individual site. Twenty years of evolution in differing environments has led to a plethora of clinical experience and effective management approaches. The goal of this review is to summarize the spectrum of HD IL-2 treatment approaches, describing various effective strategies that incorporate newer adjunctive treatments for managing the side effects of IL-2 in patients with mRCC and mM. The goal for IL-2 therapy is typically to administer the maximum number of doses of IL-2 without putting the patient at unacceptable risk for severe, irreversible toxicity. This review is based upon a consensus meeting and includes guidelines on pre-treatment screening, criteria for administration and withholding doses, and defines consensus criteria for safe administration and toxicity management. The somewhat heterogeneous best practices of 2014 will be compared and contrasted with the guidelines provided in 2001 and the package inserts from 1992 and 1998.

T-Cell Immunotherapies Targeting Histocompatibility and Tumor Antigens in Hematological Malignancies

“…A surprising complication was the occurrence of pulmonary toxicity, which is not seen following regular DLI. Although, the MiHA source protein could be detected in the lung tissue in one case, the patients had also received a conditioning regimen and post-infusion IL-2, which can be associated with pulmonary complications (111). Nonetheless, these findings are an additional argument to select MiHA with restricted expression to the hematopoietic system.…”

Immune Checkpoint Inhibition in Renal Cell Carcinoma

“…Given that signifi cant clinical experience is required to safely treat patients with HD IL-2, access is generally limited to cancer centers with experience administering this therapy and which have access to ICU-level care. However, the morbidity and mortality agent associated with HD-IL-2 has been signifi cantly reduced through the use of prophylactic antibiotics, cardiac monitoring, and more stringent patient selection [ 24 ].…”

Hepatocellular carcinoma: Prospects for natural killer cell immunotherapy

“…In vivo manipulation of NK cells by the use of injected cytokines may provide an alternative strategy to use in combination with other therapies. Direct administration of high dose IL‐2 as an infusion has been approved for use in patients with metastatic renal cancer and metastatic melanoma, but it has a narrow therapeutic window with a risk of wide ranging systemic toxic effects . IL‐15 infusions have been shown to have promising results in expanding cytotoxic CD56 bright NK subsets in vivo .…”