scholarly journals Treatment of Advanced Metastatic Melanoma

2021 ◽  
pp. 2021164S
Author(s):  
Pietro Quaglino ◽  
Paolo Fava ◽  
Luca Tonella ◽  
Marco Rubatto ◽  
Simone Ribero ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
Targeted Therapies ◽  
Checkpoint Inhibitors ◽  
Performance Status ◽  
Survival Rates ◽  
National Health System ◽  
Stage Iv ◽  
Daily Practice ◽  
Long Term Results ◽  
Melanoma Patients

The introduction in clinical practice of new drug compounds both targeted therapies anti-BRAF and checkpoint inhibitors have largely improved our potential to manage advanced metastatic melanoma patients. This has led to a significant improvement in terms of response rates and particularly in the overall survival (OS). The long-term results of trials with follow-up data of patients treated with targeted or immunotherapies reported median OS rates around 24 months, with 5-year survival rates around 35-40%. As to the drugs currently available and reimbursed by the Italian National Health System, 3 combinations of anti-BRAF/anti-MEK inhibitors are available (dabrafenib/trametinib, vemurafenib/cobimetinib and the most recently introduced encorafenib/binimetinib). As for checkpoint inhibitors, first line immunotherapy is represented by anti-PD1 blockers (nivolumab and pembrolizumab), whilst the anti-CTLA-4 ipilimumab can be used as second line immunotherapy. The decision-making factors that define the best treatment approach in stage IV patients with metastatic melanoma include the mutation pattern, performance status, high/low tumor load, brain metastases, progression pattern (low/fast), and availability of clinical trials. This review will analyze the current therapeutic tools adopted for the treatment of metastatic melanoma patients. It will then focus on the latest results obtained by novel treatments (checkpoint inhibitors and targeted therapies) which can be used in the clinical daily practice.

Prognostic factors in metastatic melanoma patients treated with biochemotherapy and maintenance immunotherapy

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 9051-9051
Author(s):  
D. R. Minor ◽  
M. Kashani-Sabet ◽  
D. Moore ◽  
C. Kim ◽  
S. S. Venna ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Metastatic Melanoma ◽  
Median Survival ◽  
Performance Status ◽  
Intensive Therapy ◽  
Stage Iv ◽  
Treatment Center ◽  
Term Survival ◽  
Melanoma Patients

9051 Background: Patients with stage IV metastatic melanoma are usually felt to be incurable with a median survival of 6.4 months and a 5-year survival of only 2%. Biochemotherapy has shown promise with long-term survival in selected patients. We felt the study of prognostic factors would determine which patients might benefit the most from this intensive therapy. Methods: 135 consecutive patients with stage IV melanoma treated with decrescendo biochemotherapy followed by maintenance immunotherapy at one melanoma treatment center were studied to determine the most important prognostic factors; these factors were then validated by analysis of 133 patients treated in a multi-center trial at other institutions. Patients were treated using the inpatient regimen of O'Day (JCO23:710s,2005 abstract). Results: Median overall survival (OS) was 16.6 months with 1-year survival of 70% and 5-year survival of 28%. Median progression-free survival (PFS) was 7.6 months with 15% progression-free at 5 years. PFS curves showed no relapses after 30 months, so remissions were durable. For OS performance status 0, normal LDH, stage M1a, and non-visceral sites of metastases were favorable prognostic factors. For PFS performance status 0, normal LDH, female sex, age <50 and stage M1a were favorable prognostic factors Multivariate analysis demonstrated two important prognostic factors for survival: normal serum LDH and the presence of either skin or nodes as one of the sites of metastatic disease. The group with normal LDH and skin or node metastases had a relatively good prognosis with median survival of 44 months and a 5-year survival of 38%. Conversely patients with elevated LDH without any skin or nodal metastases had a poor prognosis, with no long-term survivors. Conclusions: Metastatic melanoma patients treated with biochemotherapy and maintenance immunotherapy that have either a normal LDH or skin or nodes as one of their metastatic sites may have durable remissions of their disease, and this therapy should be studied further in these groups. [Table: see text]

Targeting MDSCs using ATRA: a phase I/II clinical trial combining pembrolizumab and all-trans retinoic acid for metastatic melanoma

2021 ◽  
Author(s):  
Richard Tobin ◽  
Dasha Cogswell ◽  
Victoria Vorwald ◽  
Dana Davis ◽  
Jessica Borgers ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Metastatic Melanoma ◽  
Checkpoint Inhibitors ◽  
Cell Activity ◽  
Stage Iv ◽  
Suppressor Cells ◽  
Progression Free Survival ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Melanoma Patients

Abstract Myeloid-derived suppressor cells (MDSCs) are potent suppressors of antitumor immunity and are commonly associated with poor outcomes in melanoma patients treated with immune checkpoint inhibitors. Inducing the differentiation of MDSCs using all-trans retinoic acid (ATRA) alters their activity and reduces MDSC frequency. This trial seeks to assess the safety and efficacy of combining ATRA and pembrolizumab in metastatic melanoma patients. In 24 stage IV melanoma patients, treatment with pembrolizumab Q3W plus the supplemental treatment of ATRA orally for three days surrounding each of the first four pembrolizumab infusions effectively lowered the frequency of circulating PMN-MDSCs and enhanced melanoma-specific T cell activity. The combination was well tolerated. Median progression free survival was 20.3 months, and the overall response rate was 71%, with 50% of patients experiencing a complete response. Targeting MDSCs remains a promising mechanism to enhance the efficacy of anti-PD-1 therapies and this combination merits further investigation.

scholarly journals Cancer immunotherapy does not increase the risk of death by COVID-19 in melanoma patients

2020 ◽  
Author(s):  
Maria Gonzalez-Cao ◽  
Monica Antonazas-Basa ◽  
Teresa Puertolas ◽  
Eva Munoz-Couselo ◽  
Jose Luis Manzano ◽  
...  
Keyword(s):  
Cancer Treatment ◽  
Cancer Patients ◽  
Checkpoint Inhibitors ◽  
Stage Iv ◽  
National Registry ◽  
Global Risk ◽  
Risk Of Death ◽  
Treatment Type ◽  
Melanoma Patients ◽  
Active Cancer

Background: Covid-19 pandemic by the new coronavirus SARS-Cov-2 has produced devastating effects on the health care system, affecting also cancer patient care. Data about COVID-19 infection in cancer patients are scarce, and they point out a higher risk of complications due to the viral infection in this population. Moreover, cancer treatments could increase viral complications, specially those treatments based on the use of immunotherapy with checkpoints antibodies. There are no clinical data about the safety of immune check point antibodies in cancer patients when they become infected by SARS-CoV-2. As checkpoint inhibitors, mainly anti PD-1 and anti CTLA-4 antibodies, are an effective treatment for most melanoma patients, avoiding their use during the pandemic could lead to a decrease in the chances of curing melanoma. Methods: In Spain we have started a national registry of melanoma patients infected by SARS-Cov-2 since April 1st, 2020. A retrospective analysis of patients included in the Spanish registery has been performed weekly since the activation of the study. Interim analysis shows unexpected findings about cancer treatment safety in SARS-Cov-2 infected melanoma patients, so a rapid communication to the scientific community is mandatory Results: Fifty patients have been included as of May 17th, 2020. Median age is 69 years (range 6 to 94 years), 27 (54%) patients are males and 36 (70%) patients have stage IV melanoma. Twenty-two (44%) patients were on active anticancer treatment with anti PD-1 antibodies, 16 (32%) patients were on treatment with BRAF plus MEK inhibitors and 12 (24%) patients were not on active cancer treatment. COVID-19 episode has been resolved in 43 cases, including 30 (70%) patients cured, four (9%) patients that have died due to melanoma progression, and nine (21%) patients that have died from COVID-19. Mortality rates from COVID-19 according to melanoma treatment type were 16%, 15% and 36% for patients on immunotherapy, targeted drugs, and for those that were not undergoing active cancer treatment, respectively. Conclusion: These preliminary findings show that the risk of death in those patients undergoing treatment with anti PD-1 antibodies does not exceed the global risk of death in this population. These results could be relevant in order to select melanoma therapy during the COVID-19 pandemic  

Toxicity, response, and survival in older adults with metastatic melanoma treated with checkpoint inhibitors.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9544-9544
Author(s):  
Nienke A De Glas ◽  
Esther Bastiaannet ◽  
Frederiek van den Bos ◽  
Simon Mooijaart ◽  
Astrid Aplonia Maria Van Der Veldt ◽  
...  
Keyword(s):  
Older Adults ◽  
Overall Survival ◽  
Metastatic Melanoma ◽  
Older Patients ◽  
Regression Models ◽  
Checkpoint Inhibitors ◽  
Performance Status ◽  
Toxicity Response ◽  
Grade 3 ◽  
The Impact

9544 Background: Checkpoint inhibitors have strongly improved survival of patients with metastatic melanoma. Trials suggest no differences in outcomes between older and younger patients, but only relatively young patients with a good performance status were included in these trials. The aim of this study was to describe treatment patterns and outcomes of older adults with metastatic melanoma, and to identify predictors of outcome. Methods: We included all patients aged ≥65 years with metastatic melanoma between 2013 and 2020 from the Dutch Melanoma Treatment registry (DMTR), in which detailed information on patients, treatments and outcomes is available. We assessed predictors of grade ≥3 toxicity and 6-months response using logistic regression models, and melanoma-specific and overall survival using Cox regression models. Additionally, we described reasons for hospital admissions and treatment discontinuation. Results: A total of 2216 patients were included. Grade ≥3 toxicity did not increase with age, comorbidity or WHO performance status, in patients treated with monotherapy (anti-PD1 or ipilimumab) or combination treatment. However, patients aged ≥75 were admitted more frequently and discontinued treatment due to toxicity more often. Six months-response rates were similar to previous randomized trials (40.3% and 43.6% in patients aged 65-75 and ≥75 respectively for anti-PD1 treatment) and were not affected by age or comorbidity. Melanoma-specific survival was not affected by age or comorbidity, but age, comorbidity and WHO performance status were associated with overall survival in multivariate analyses. Conclusions: Toxicity, response and melanoma-specific survival were not associated with age or comorbidity status. Treatment with immunotherapy should therefore not be omitted solely based on age or comorbidity. However, the impact of grade I-II toxicity in older patients deserves further study as older patients discontinue treatment more frequently and receive less treatment cycles.[Table: see text]

scholarly journals Body mass index (BMI) and outcome of metastatic melanoma patients receiving targeted therapy and immunotherapy: a multicenter international retrospective study

2020 ◽  
Vol 8 (2) ◽  
pp. e001117
Author(s):  
Piotr Rutkowski ◽  
Alice Indini ◽  
Matilde De Luca ◽  
Barbara Merelli ◽  
Anna Mariuk-Jarema ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Metastatic Melanoma ◽  
Risk Reduction ◽  
Body Mass ◽  
Regression Models ◽  
Cox Regression ◽  
Checkpoint Inhibitors ◽  
Performance Status ◽  
Prognostic Role ◽  
First Line

BackgroundObesity is a risk factor for malignancy; however, its prognostic role in patients with metastatic melanoma is controversial. We aim to investigate the prognostic role of body mass index (BMI) in patients with metastatic melanoma receiving mitogen-activated pathway kinase inhibitors (MAPKi), immune checkpoint inhibitors (ICIs) alone or their sequence.MethodsData on patients with metastatic melanoma receiving ≥1 line of systemic treatment were retrieved from prospectively collected databases. Progression-free survival (PFS) and overall survival (OS) were analyzed by means of multivariable stratified Cox regression models; disease control rate (DCR) was analyzed by multivariable stratified logistic regression models. Subgroup analyzes according to the type of treatments received, and in BRAF-mutated patients were pre-planned. All multivariable models included BMI, age, gender, American Joint Committee on Cancer stage, performance status, lactate dehydrogenase and treatment sequencing strategy as covariates.ResultsBetween November 2010 and November 2018, 688 patients from three Italian and two Polish centers were enrolled. 379 (57%) patients had M1c/d disease, 273 (41%) were female and the mean BMI was 27.1 (SD=4.9). Considering first-line treatment, 446 patients (66.8%) received ICIs and 222 MAPKi. No impact of BMI on OS was detected either considering the first line of ICIs, or ICIs sequencing (HR=1.02, 95% CI: 0.99 to 1.05, p=0.202, and HR=1.02, 95% CI: 0.99 to 1.04, p=0.237, respectively). A late effect of BMI on OS was found in patients treated with MAPKi: for five units increment, a 51% of risk reduction at 18 months and a 76% of risk reduction at 30 months were observed. No significant effect of BMI on PFS and DCR was found in any of the subgroup analyzes.ConclusionIn patients with metastatic melanoma receiving ICIs, there is no impact of BMI on DCR, PFS and OS. The late prognostic effect of BMI in patients treated with MAPKi should be considered hypothesis generating and needs to be further investigated.

The current role of systemic therapy in the management of Malignant Melanoma of the skin: a literature review

2004 ◽  
Vol 4 (4) ◽  
pp. 161-175 ◽  
Author(s):  
Elizabeth Reeves ◽  
P. Bridge ◽  
R. M. Appleyard
Keyword(s):  
Clinical Trials ◽  
Literature Review ◽  
Metastatic Melanoma ◽  
Systemic Therapy ◽  
Survival Rates ◽  
Success Rates ◽  
Systemic Treatments ◽  
Melanoma Patients ◽  
Disease Free

Melanoma patients can be split into two main categories that have different aims for treatment; localised disease with either intermediate or high-risk of recurrence after surgery, and metastatic disease. Over the past decade, there have been many clinical trials looking at improving the success rates for localised and metastatic melanoma with alternative systemic treatments, namely immunotherapy, biochemotherapy and vaccines. This literature review summarises the clinical trials for each form of systemic treatment in localised and metastatic melanoma and assesses the effectiveness of each by an evaluation and comparison of relevant clinical trials for each systemic modality. The main objective was to assess whether alternative forms of systemic therapy have improved the disease free and overall survival rates achieved with chemotherapy.

Sarcoidosis-like syndrome and lymphadenopathy due to checkpoint inhibitors

2016 ◽  
Vol 23 (8) ◽  
pp. 620-624 ◽  
Author(s):  
Belal Firwana ◽  
Rahul Ravilla ◽  
Mihir Raval ◽  
Laura Hutchins ◽  
Fade Mahmoud
Keyword(s):  
Cell Death ◽  
Adverse Event ◽  
T Cell ◽  
Metastatic Melanoma ◽  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Stage Iv ◽  
Stage Iii ◽  
Lymphocyte Antigen

Immunotherapy with checkpoint inhibitors has revolutionized the management of metastatic melanoma. These checkpoints, namely the cytotoxic T lymphocyte antigen 4 and the programmed T cell death 1 receptor, possess an inhibitory effect on the T cell function. Pharmacologic inhibition of cytotoxic T lymphocyte antigen 4 with ipilimumab and programmed T cell death 1 with either pembrolizumab or nivolumab has resulted in long-term sustained responses among patients with metastatic melanoma. The adverse events of these medications are predominantly immune related. Sarcoidosis-like syndrome/lymphadenopathy represents a challenging adverse event to the oncologist as it can be mistaken for progressive disease. Hence, awareness of such adverse event and obtaining a biopsy of the enlarged lymph nodes will confirm the diagnosis and avoid the unnecessary change of current therapies for those with stage IV disease or adding new ones for those with stage III disease. We report three cases of immunotherapy-related sarcoidosis-like syndrome/lymphadenopathy; two cases occurred during adjuvant ipilimumab for stage III surgically resected melanoma and one case during pemprolizumab for stage IV metastatic melanoma.

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