V. Kruse MD, PhD

The ION-Ghent guidelines for the management of immune related adverse events (irAE’s)

SUMMARY

Checkpoint inhibitors targeting CTLA4, PD1 and PD-L1 have become a part of the daily clinical practice in the management of stage IV melanoma, renal cell carcinoma (RCC), non-small cell lung cancer (NSCLC) and Hodgkin-lymphoma patients. While these agents can elicit strong anti-tumour immune responses, they can also generate immune related adverse events, which can become life threatening if not detected and managed promptly. At the University Hospital Ghent, we created a working group of organ specialists with specific experience in dealing with immune related adverse events. This initiative is part of ION (Immuno-Oncology-Network) Ghent. In this paper we would like to share our institutional guidelines for the clinical care of patients treated with checkpoint-inhibitors with the Belgian Oncology Community.

(BELG J MED ONCOL 2017;11(6):265–276)

Indoleamine 2, 3-dioxygenase (IDO) inhibition for cancer therapy

Indoleamine 2,3-dioxygenase (IDO, also referred to as IDO1) has been demonstrated to be a normal endogenous mechanism of acquired peripheral immune tolerance in vivo. This manuscript reviews the currently available data on the role of IDO in cancer and the current results obtained with IDO inhibition in clinical trials in humans. Preliminary results with IDO inhibitors, usually combined with other anti-cancer drugs, seem encouraging. Further studies are needed to clarify the conditions in which IDO inhibitors can be of value as an anti-cancer strategy. In addition, further research should address whether the expression of IDO in tissue or blood can be a marker to select patients who can benefit most from IDO inhibition.

Highlights in melanoma

Summary

Although immunotherapy for melanoma caught a lot of interest at this year ESMO congress, some interesting new data on targeted therapies were presented as well. We have selected 10 abstracts, which, to our opinion, deserve some extra attention.

(BELG J MED ONCOL 2016;10(8):314–18)

Treatment of metastatic melanoma: an update on the Belgian situation

Summary

The therapeutic landscape for the treatment of metastatic melanoma has been changing dramatically over the last years. Given the availability of several promising drugs, choosing the best sequence for the individual patient has become a challenge. Immunotherapy by means of checkpoint-inhibitors, such as the anti-CTLA4-antibody ipilimumab and the anti-PD1-antibodies nivolumab and pembrolizumab, has demonstrated unprecedented long-term survival rates. When prescribing an immunotherapeutic agent, the clinician should be aware that the patient is at risk of developing an immune-related adverse event, especially when anti-CTLA4 and anti-PD1 are administered together. A promising future strategy to increase response rates of the checkpoint-inhibitors is combining them with radiotherapy. Hereby an abscopal effect is induced, reducing both irradiated and non-irradiated tumour lesions. Another therapeutic strategy is based on the presence of a BRAF mutation among approximately 40–50% of melanoma patients. For those patients, combined therapy with a BRAF inhibitor and a MEK inhibitor is valued to be a convincing regimen, especially in case of a high disease burden, elevated LDH and a performance status of 1–2. In contrast, T-VEC is a valuable therapeutic option for patients with limited disease.

(BELG J MED ONCOL 2016;10(6):215–222)

An update on the systemic treatment of renal cell cancer

Renal cell carcinoma is a common malignancy affecting men and women sporadically or as part of an inherited syndrome. Upregulation of VEGF and other growth factors due to accumulation of HIF in combination with an activation of the mTOR pathway are known to be important parts of the pathogenesis. These signaling pathways are therapeutic targets of monoclonal antibodies, small-molecules kinase inhibitors (TKI’s) and mTOR-pathway inhibitors and currently constitute the mainstay of metastatic RCC treatment. During the last decade, treatment options for patients with advanced renal cell carcinoma, a disease resistant to cytotoxic chemotherapy, have improved significantly with increasing survival rates. Several clinical trials are ongoing and new results are expected in the coming years. In Belgium, three TKI’s, two mTOR-inhibitors and one anti-VEGF monoclonal antibody in combination with IFN-α are reimbursed for the treatment of advanced renal cell carcinoma. Sunitinib can be administered in first line and everolimus from second line on to patients with low- or intermediate risk disease. Therapy with bevacizumab/IFN-α is an alternative first line option. Temsirolimus is an option in first line for patients with high risk disease. Sorafenib has shown positive results in patients pretreated with cytokines. Recently, pazopanib has become available as a first line treatment for patients with advanced renal cell carcinoma.

(BELG J MED ONCOL 2012;6:13–21)