Use of immune checkpoint inhibitors prolonged overall survival in a Japanese population of advanced malignant melanoma patients: Retrospective single institutional study

ObjectiveTo assess the relative effectiveness and cost-effectiveness of seven new drugs (cobimetinib, dabrafenib, ipilimumab, nivolumab, pembrolizumab, trametinib and vemurafenib) used for treatment of patients with advanced malignant melanoma in the Norwegian setting.DesignA multiple technology assessment.PatientsPatients with advanced malignant melanoma aged 18 or older.Data sourcesA systematic search for randomised controlled trials in relevant bibliographic databases.MethodsWe performed network meta-analyses using both direct and indirect evidence with dacarbazine as a common comparator. We ranked the different treatments in terms of their likelihood of leading to the best results for each endpoint. The cost-utility analysis was based on a probabilistic discrete-time Markov cohort model. The model calculated the costs and quality-adjusted life years (QALYs) with different treatment strategies from a healthcare perspective. Sensitivity analysis was performed by means of Monte Carlo simulation.ResultsMonotherapies with a programmed cell death 1 (PD-1) immune-checkpoint-inhibitor had a higher probability of good performance for overall survival than monotherapies with ipilimumab or BRAF/MEK inhibitors. The combination treatments had all similar levels of effectiveness to the PD-1 immune-checkpoint-inhibitors.PD-1 immune-checkpoint-inhibitors are more effective and more costly compared with ipilimumab in monotherapy. Nivolumab in combination with ipilimumab had higher costs and the same level of effectiveness as the PD-1 immune-checkpoint-inhibitors in monotherapy.BRAF/MEK inhibitor combinations (dabrafenib and trametinib or vemurafenib and cobimetinib) had both similar effectiveness and cost-effectiveness; however, the combination therapies are more likely to give higher quality adjusted life year gains than BRAF or MEK inhibitor monotherapies, but to a higher cost.ConclusionsNone of the drugs investigated can be considered cost-effective at what has normally been considered a reasonable willingness-to-pay (WTP) in Norway. Price reductions (from the official list prices) in the region of 63%–84% would be necessary for these drugs to be cost-effective at a WTP of €55 850 per QALY.

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Successful Treatment of a Patient with anti-PD1 Antibody-Resistant Advanced Mucosal Melanoma with Nivolumab, Ipilimumab plus Denosumab Combination Therapy

Case Reports in Oncology ◽

10.1159/000506327 ◽

2020 ◽

Vol 13 (1) ◽

pp. 271-275 ◽

Cited By ~ 1

Author(s):

Taku Fujimura ◽

Yumi Kambayashi ◽

Kentaro Ohuchi ◽

Ryo Amagai ◽

Yota Sato ◽

...

Keyword(s):

Malignant Melanoma ◽

Combination Therapy ◽

Nasal Cavity ◽

Immune Checkpoint ◽

Cutaneous Melanoma ◽

Japanese Population ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Mucosal Melanoma ◽

Mutation Burden

Since the incidence of mucosal melanoma is higher in the Japanese population compared to Caucasians, and since mucosal melanoma possesses a lower mutation burden compared to cutaneous melanoma, the efficacy of anti-PD1 antibody (Ab) monotherapy for mucosal melanoma is limited. Therefore, other targeting molecules that enhance the anti-tumor effects of immune checkpoint inhibitors are needed. In this report, we present a case with anti-PD1 Ab-resistant recurrent malignant melanoma of the nasal cavity successfully treated with nivolumab, ipilimumab plus denosumab combination therapy.

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Predictive and prognostic effect of ABO blood group on immune checkpoint inhibitors

Cancer Biomarkers ◽

10.3233/cbm-210455 ◽

2021 ◽

pp. 1-8

Author(s):

Yakup Ergun ◽

Selin Akturk Esen ◽

Murat Bardakci ◽

Gokhan Ucar ◽

Ziya Kalkan ◽

...

Keyword(s):

Malignant Melanoma ◽

Blood Group ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Blood Groups ◽

Abo Blood Group ◽

Blood Group System ◽

Advanced Malignant Melanoma ◽

The Relationship

BACKGROUND: The relationship of the ABO blood group system with the immune response is known, but its relationship with immune checkpoint inhibitors (ICIs) has not been clearly investigated until now. OBJECTIVE: In this study, the relationship between different blood groups and nivolumab treatment response in patients with advanced malignant melanoma was investigated. METHODS: The data of patients who used nivolumab for advanced malignant melanoma between April 2018 and April 2021 were retrospectively reviewed. RESULTS: A total of 73 patients were included in the study. In the progression-free survival (PFS) analysis according to blood groups, it was 3.9 months, 16.1 months, 20.0 months and 3.0 months for A, B, AB and O, respectively (p= 0.1). Overall survival (OS) analysis according to blood groups was 5.1 months, 25.0 months, 20.0 months and 9.3 months for A, B, AB and O, respectively (p= 0.1). The B antigen group (B or AB) had significantly longer PFS and OS than the non-B antigen group (A or O) (16.1 vs. 3.5 months for PFS, respectively, p= 0.03; 20.0 vs. 7.4 months for OS, respectively, p= 0.02). CONCLUSIONS: The presence of B antigen provides a significant advantage in terms of survival in patients using ICIs for advanced melanoma.

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Long-term Overall Survival and Predictors in Anti–PD-1-naive Melanoma Patients With Brain Metastases Treated With Immune Checkpoint Inhibitors in the Real-world Setting

Journal of Immunotherapy ◽

10.1097/cji.0000000000000385 ◽

2021 ◽

Vol Publish Ahead of Print ◽

Author(s):

Girish S. Naik ◽

Elizabeth I. Buchbinder ◽

Justine V. Cohen ◽

Michael P. Manos ◽

Alistair E.W. Johnson ◽

...

Keyword(s):

Overall Survival ◽

Brain Metastases ◽

Real World ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

The Real ◽

Real World Setting ◽

Melanoma Patients

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PCN29 Time to Next Treatment As a Candidate Surrogate Endpoint for Overall Survival in Previously Untreated Advanced Melanoma Patients Treated with Immune-Checkpoint Inhibitors

Value in Health ◽

10.1016/j.jval.2020.08.166 ◽

2020 ◽

Vol 23 ◽

pp. S426

Author(s):

S. Branchoux ◽

C.L. Sofeu ◽

A.F. Gaudin ◽

M. Kurt ◽

A. Moshyk ◽

...

Keyword(s):

Overall Survival ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Surrogate Endpoint ◽

Advanced Melanoma ◽

Melanoma Patients

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

BMJ Case Reports ◽

10.1136/bcr-2021-241981 ◽

2021 ◽

Vol 14 (5) ◽

pp. e241981

Author(s):

Ansgar Heck ◽

Anna K Winge-Main

Keyword(s):

Malignant Melanoma ◽

Adrenal Insufficiency ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Adrenal Crisis ◽

Suspected Case ◽

Acth Deficiency ◽

Melanoma Patients ◽

Central Adrenal Insufficiency

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.

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