Long-term outcomes of stage IIB-IV melanoma patients: nationwide data from Norway.

Aim: This study was performed to investigate the characteristics and overall survival (OS) of patients with completely resected stage IIB-IV cutaneous melanoma identified in the Cancer Registry of Norway. Methods: A retrospective cohort study of all adult patients with stage ≥IIB cutaneous melanoma was performed in Norway (January 2008 to December 2018), excluding patients with stage IV melanoma without evidence of surgery. Results: 5-year OS varied by stage (IIB 65%, IIC 38%, IIIA 79%, IIIB 66%, IIIC 52%, IIID 37% and IV 39%). Adjusted Cox models showed that stage IIIA and IIIB patients showed similar survival to stage IIB patients (hazard ratio [95% CI]: IIIA 0.67 [0.44-1.04]; IIIB 1.18 [0.96-1.45]), while all other stages had lower survival than IIB. Conclusion: Survival for stage II patients, particularly IIC, can be poor and in some cases worse than patients with more advanced stage melanoma. Our data highlight an unmet need for effective adjuvant treatment options among stage IIB/C patients.

The number of people diagnosed with skin cancer cutaneous melanoma is increasing globally, with Norway having the second highest rate of death due to melanoma in the world. The stage of disease (how much the tumor has spread) determines which treatment is most effective. While early-stage disease is typically considered of low risk, people diagnosed at this stage have a high risk of disease recurrence and a similar chance of survival to those diagnosed at a later disease stage. By researching how long people with melanoma survive based on their disease stage, we gain greater insight into which groups of patients may have an unmet need for therapy. This study aimed to understand how long patients with melanoma in Norway survive after diagnosis, based on their disease stage at diagnosis. The study used patient data from the Cancer Registry of Norway and included only the patients diagnosed with at least stage IIB melanoma from January 2008 to December 2018, unless they had stage IV disease that had not been treated with surgery. This study found that the proportion of patients who survived to 5 years was dependent on the disease stage at diagnosis; however, patients in earlier stages had similar survival to those in later (although not very late) stages of disease. This research shows that patients diagnosed with early-stage melanoma in Norway have an unmet need for treatment options following surgery that address the severity of their risk. This research may help inform decision-making around which treatments patients with early-stage melanoma have access to.

Targeting Telomerase with an HLA Class II-Restricted TCR for Cancer Immunotherapy.

T cell receptor (TCR)-engineered T cell therapy is a promising cancer treatment approach. Human telomerase reverse transcriptase (hTERT) is overexpressed in the majority of tumors and a potential target for adoptive cell therapy. We isolated a novel hTERT-specific TCR sequence, named Radium-4, from a clinically responding pancreatic cancer patient vaccinated with a long hTERT peptide. Radium-4 TCR-redirected primary CD4+ and CD8+ T cells demonstrated in vitro efficacy, producing inflammatory cytokines and killing hTERT+ melanoma cells in both 2D and 3D settings, as well as malignant, patient-derived ascites cells. Importantly, T cells expressing Radium-4 TCR displayed no toxicity against bone marrow stem cells or mature hematopoietic cells. Notably, Radium-4 TCR+ T cells also significantly reduced tumor growth and improved survival in a xenograft mouse model. Since hTERT is a universal cancer antigen, and the very frequently expressed HLA class II molecules presenting the hTERT peptide to this TCR provide a very high (>75%) population coverage, this TCR represents an attractive candidate for immunotherapy of solid tumors.

Melanoma - investigation and primary treatment. / Melanom ­ utredning og primærbehandling.

Melanoma is a relatively common diagnosis, both in the primary and specialist health service. Ongoing research and new evidence base means that the recommendations for investigation and treatment are continually changing. This can lead to uncertainty among doctors who do not treat this patient group regularly. In this clinical review we give a summary of the latest recommendations, primarily aimed at general practitioners, dermatologists and doctors in local hospitals.

T cell receptor therapy against melanoma-Immunotherapy for the future?

Malignant melanoma has seen monumental changes in treatment options the last decade from the very poor results of dacarbazine treatment to the modern-day use of targeted therapies and immune checkpoint inhibitors. Melanoma has a high mutational burden making it more capable of evoking immune responses than many other tumours. Even when considering double immune checkpoint blockade with anti-CTLA-4 and anti-PD-1, we still have far to go in melanoma treatment as 50% of patients with metastatic disease do not respond to current treatment. Alternative immunotherapy should therefore be considered. Since melanoma has a high mutational burden, it is considered more immunogenic than many other tumours. T cell receptor (TCR) therapy could be a possible way forward, either alone or in combination, to improve the response rates of this deadly disease. Melanoma is one of the cancers where TCR therapy has been frequently applied. However, the number of antigens targeted remains fairly limited, although advanced personalized therapies aim at also targeting private mutations. In this review, we look at possible aspects of targeting TCR therapy towards melanoma and provide an implication of its use in the future.

Silent, isolated ACTH deficiency in malignant melanoma patients treated with immune checkpoint inhibitors.

Treatment with immune checkpoint inhibitors (ICI) has drastically improved the prognosis for melanoma patients, but immune-mediated adverse events can occur in any organ, including the pituitary. In ICI-induced hypophysitis, lymphocytic infiltration and hypersensitivity reactions cause headache and pituitary deficiency. Most cases with ICI-induced hypophysitis develop central adrenal insufficiency. Here, we describe three patients treated with anticytotoxic T-lymphocyte-associated protein 4 (ipilimumab) for metastatic malignant melanoma: case 1 was asymptomatic when hypocortisolism was suspected; case 2 had symptoms of hypocortisolism and suspected severe systemic infection; case 3 had unspecific fatigue. In all cases, routine cortisol measurements and clinical suspicion (cases 2 and 3) led to the diagnosis of adrenocortical hormone (ACTH) deficiency and thereby central adrenal insufficiency. Undiagnosed and untreated, central adrenal insufficiency results in adrenal crisis. In patients treated with ICI, particularly, ipilimumab, hypophysitis and ACTH deficiency must be considered if morning cortisol is low or unspecific clinical symptoms of hypocortisolism are present.