Failure of adjuvant treatment for malignant melanoma - what next?

BACKGROUND: The possibilities of adjuvant therapy of malignant melanoma have significantly expanded in recent years. Based on the results of clinical studies, immunotherapy represented by checkpoint inhibitors (ipilimumab, pembrolizumab, nivolumab) and targeted therapies (dabrafenib plus trametinib) in patients with a proven mutation in the BRAF gene were included in the treatment protocols. In the Czech Republic, nivolumab and combination therapy of dabrafenib with trametinib are currently available for clinical practice. However, the question remains how to proceed if relapse or generalization occurs after the adjuvant treatment. The following case study describes one of possible solutions. CASE REPORT: The article presents the failure of adjuvant nivolumab immunotherapy in a patient with locally advanced stage IIIC malignant melanoma. Ipilimumab has been selected as a treatment choice and demonstrated its efficacy. However, its administration was associated with immune-related side effects. These were dia-gnosed and successfully treated in the internal department in close cooperation with our department of oncology. CONCLUSION: Although adjuvant therapy has significantly reduced a risk of disease relapse, there is a cohort of patients in whom adjuvant therapy fails. Failure may occur after the end of the therapy or, as in our case, during the therapy. Based on currently available data, it is not possible to unambiguously choose the optimal procedure after adjuvant therapy failure. Currently, there is no other way than following clinical experience and reimbursement regulations, or enrolling the patient in a clinical trial. Immune-related adverse effects require particular attention as they are unique due to their mechanism of origin and often require a multidisciplinary approach.

Nivolumab induced encephalopathy in a man with metastatic renal cell cancer: a case report.

BACKGROUND: Great progress has recently been made in the treatment of metastatic renal cell carcinoma, including the introduction of nivolumab, an immune checkpoint inhibitor. Despite promising results, this treatment brings a completely new spectrum of adverse events, distinct from those experienced with small-molecule kinase inhibitors. Neurologic immune-related adverse events may be serious and potentially life-threatening complications requiring immediate immunosuppressive therapy. Only a few cases of immune-related encephalitis induced by checkpoint inhibitors have been described and the data regarding the management of this serious adverse event are limited. CASE PRESENTATION: We report the case of a 63-year-old white man with metastatic renal cancer who developed severe chorea-like dyskinesia during nivolumab therapy. The findings on brain magnetic resonance imaging and flow cytometry of cerebrospinal fluid, and the positivity of anti-paraneoplastic antigen Ma2 immunoglobuline G class autoantibodies were consistent with a diagnosis of immune-related encephalitis. High-dose intravenous corticosteroid therapy was started immediately, with no signs of improvement, even when infliximab was added. Our patient refused further hospitalization and was discharged. Three weeks later, he presented with signs of severe urosepsis. Despite intensive treatment, he died 4 days after admission. CONCLUSIONS: The management of less frequent immune-related adverse events has not been fully established and more information is required to provide uniform recommendations. Immune-related encephalitis is a severe and potentially fatal complication requiring immediate hospital admission and extensive immunosuppressive therapy. The examination of cerebrospinal fluid for paraneoplastic antibodies, such as anti-N-methyl-D-aspartate receptor and anti-Ma2 antibodies, in order to distinguish autoimmune etiology from other possible causes is essential and highly recommended.