Increases in Serum TARC/CCL17 Levels Are Associated with Progression-Free Survival in Advanced Melanoma Patients in Response to Dendritic Cell-Based Immunotherapy

2009 ◽  
Vol 29 (5) ◽  
pp. 657-664 ◽  
Author(s):  
Andrew N. Cornforth ◽  
Gregory J. Lee ◽  
Abner W. Fowler ◽  
Denysha J. Carbonell ◽  
Robert O. Dillman
Keyword(s):  
Dendritic Cell ◽  
Progression Free Survival ◽  
Advanced Melanoma ◽  
Free Survival ◽  
Melanoma Patients

scholarly journals Antibiotics are associated with decreased progression-free survival of advanced melanoma patients treated with immune checkpoint inhibitors

2019 ◽  
Vol 8 (4) ◽  
pp. e1568812 ◽  
Author(s):  
Arielle Elkrief ◽  
Layal El Raichani ◽  
Corentin Richard ◽  
Meriem Messaoudene ◽  
Wiam Belkaid ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Progression Free Survival ◽  
Advanced Melanoma ◽  
Free Survival ◽  
Melanoma Patients

scholarly journals Circulating tumor DNA (ctDNA) detection is associated with shorter progression-free survival in advanced melanoma patients

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Gabriella Taques Marczynski ◽  
Ana Carolina Laus ◽  
Mariana Bisarro dos Reis ◽  
Rui Manuel Reis ◽  
Vinicius de Lima Vazquez
Keyword(s):  
Somatic Mutations ◽  
Limit Of Detection ◽  
Progression Free Survival ◽  
Circulating Tumor Dna ◽  
Advanced Melanoma ◽  
Plasma Samples ◽  
Free Survival ◽  
Melanoma Patients ◽  
Digital Polymerase Chain Reaction ◽  
Tumor Dna

Abstract BRAF, NRAS and TERT mutations occur in more than 2/3 of melanomas. Its detection in patient’s blood, as circulating tumor DNA (ctDNA), represents a possibility for identification and monitoring of metastatic disease. We proposed to standardize a liquid biopsy platform to identify hotspot mutations in BRAF, NRAS and TERT in plasma samples from advanced melanoma patients and investigate whether it was associated to clinical outcome. Firstly, we performed digital polymerase chain reaction using tumor cell lines for validation and determination of limit of detection (LOD) of each assay and screened plasma samples from healthy individuals to determine the limit of blank (LOB). Then, we selected 19 stage III and IV patients and determined the somatic mutations status in tumor tissue and track them in patients’ plasma. We established a specific and sensitive methodology with a LOD ranging from 0.13 to 0.37%, and LOB ranging from of 0 to 5.201 copies/reaction. Somatic mutations occurred in 17/19 (89%) patients, of whom seven (41%) had ctDNA detectable their paired plasma. ctDNA detection was associated with shorter progression free survival (p = 0.01). In conclusion, our data support the use of ctDNA as prognosis biomarker, suggesting that patients with detectable levels have an unfavorable outcome.

scholarly journals The association between immune-related adverse events and survival outcomes in Asian patients with advanced melanoma receiving anti-PD-1 antibodies

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Chiao-En Wu ◽  
Chan-Keng Yang ◽  
Meng-Ting Peng ◽  
Pei-Wei Huang ◽  
Ching-Fu Chang ◽  
...  
Keyword(s):  
Adverse Events ◽  
Clinical Outcomes ◽  
Checkpoint Inhibitors ◽  
Progression Free Survival ◽  
Advanced Melanoma ◽  
Survival Outcomes ◽  
Free Survival ◽  
Asian Patients ◽  
Melanoma Patients ◽  
Experienced Grade

Abstract Background The association between immune-related adverse events (irAEs) and survival outcomes in patients with advanced melanoma receiving therapy with immune checkpoint inhibitors (ICIs) has not been well established, particularly in Asian melanoma. Methods We retrospectively reviewed 49 melanoma patients undergoing therapy with ICIs (anti-PD-1 monotherapy), and analyzed the correlation between irAEs and clinical outcomes including progression-free survival (PFS) and overall survival (OS). Results: Overall, the patients who experienced grade 1–2 irAEs had longer PFS (median PFS, 4.6 vs. 2.5 months; HR, 0.52; 95% CI: 0.27–0.98; p = 0.042) and OS (median OS, 15.2 vs. 5.7 months; HR, 0.50; 95% CI: 0.24–1.02; p = 0.058) than the patients who did not experience irAEs. Regarding the type of irAE, the patients with either skin/vitiligo or endocrine irAEs showed better PFS (median PFS, 6.1 vs. 2.7 months; HR, 0.40, 95% CI: 0.21–0.74; p = 0.003) and OS (median OS, 18.7 vs. 4.5 months; HR, 0.34, 95% CI: 0.17–0.69, p = 0.003) than patients without any of these irAEs. Conclusions Melanoma patients undergoing anti-PD-1 monotherapy and experiencing mild-to-moderate irAEs (grade 1–2), particularly skin (vitiligo)/endocrine irAEs had favorable survival outcomes. Therefore, the association between irAEs and the clinical outcomes in melanoma patients undergoing anti-PD-1 ICIs may be severity and type dependent.

scholarly journals The pan-immune-inflammation value and systemic immune-inflammation index in advanced melanoma patients under immunotherapy

2022 ◽  
Author(s):  
L. Susok ◽  
S. Said ◽  
D. Reinert ◽  
R. Mansour ◽  
C. H. Scheel ◽  
...  
Keyword(s):  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Progression Free Survival ◽  
Advanced Melanoma ◽  
Stage I ◽  
Stage Iii ◽  
Free Survival ◽  
Best Response ◽  
Melanoma Patients ◽  
Immune Inflammation

Abstract Purpose To evaluate the pan-immune-inflammation value (PIV) and systemic immune-inflammation index (SII) in patients with cutaneous melanoma (CM) under immune checkpoint inhibitor (ICI) therapy. Methods PIV and SII were calculated before the start of ICI therapy and at time of progression/death in patients with metastatic CM (stage III/IV). Sex–age-matched CM patients in stage I/II and healthy subjects (HC) served as controls. Results The median PIV of stage III/IV patients was significantly (P = 0.0011) higher than in stage I/II patients and HC. SII was significantly (P = 0.00044) lower in HC than in CM patients. At baseline, PIV and SII did significantly correlate with lactate dehydrogenase (P = 0.045/0.017). However, ROC curve statistics revealed that SII and PIV were not significantly associated with clinical parameters, including best response to ICI treatment (P = 0.87/0.64), progression-free survival (P = 0.73/0.91), and melanoma-specific survival (P = 0.13/0.17). Moreover, there were no significant changes of PIV and SII from baseline to progression/death (P = 0.38/0.52). Conclusions Even though both immune-inflammation biomarkers showed some power to differentiate between CM stages and HC, respectively, PIV and SII seem not to be significant predictors for clinical outcome measures of CM patients under ICI therapy.

scholarly journals Phase II trial of the IDO pathway inhibitor indoximod plus pembrolizumab for the treatment of patients with advanced melanoma

2021 ◽  
Vol 9 (6) ◽  
pp. e002057
Author(s):  
Yousef Zakharia ◽  
Robert R McWilliams ◽  
Olivier Rixe ◽  
Joseph Drabick ◽  
Montaser F Shaheen ◽  
...  
Keyword(s):  
Phase Ii ◽  
Single Agent ◽  
Objective Response ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Complete Response ◽  
Advanced Melanoma ◽  
Free Survival ◽  
Programmed Death ◽  
Evaluable Population

BackgroundThe indoleamine 2,3-dioxygenase (IDO) pathway is a key counter-regulatory mechanism that, in cancer, is exploited by tumors to evade antitumor immunity. Indoximod is a small-molecule IDO pathway inhibitor that reverses the immunosuppressive effects of low tryptophan (Trp) and high kynurenine (Kyn) that result from IDO activity. In this study, indoximod was used in combination with a checkpoint inhibitor (CPI) pembrolizumab for the treatment for advanced melanoma.MethodsPatients with advanced melanoma were enrolled in a single-arm phase II clinical trial evaluating the addition of indoximod to standard of care CPI approved for melanoma. Investigators administered their choice of CPI including pembrolizumab (P), nivolumab (N), or ipilimumab (I). Indoximod was administered continuously (1200 mg orally two times per day), with concurrent CPI dosed per US Food and Drug Administration (FDA)-approved label.ResultsBetween July 2014 and July 2017, 131 patients were enrolled. (P) was used more frequently (n=114, 87%) per investigator’s choice. The efficacy evaluable population consisted of 89 patients from the phase II cohort with non-ocular melanoma who received indoximod combined with (P).The objective response rate (ORR) for the evaluable population was 51% with confirmed complete response of 20% and disease control rate of 70%. Median progression-free survival was 12.4 months (95% CI 6.4 to 24.9). The ORR for Programmed Death-Ligand 1 (PD-L1)-positive patients was 70% compared with 46% for PD-L1-negative patients. The combination was well tolerated, and side effects were similar to what was expected from single agent (P).ConclusionIn this study, the combination of indoximod and (P) was well tolerated and showed antitumor efficacy that is worth further evaluation in selected patients with advanced melanoma.

scholarly journals Advanced melanoma, a pharmacological evaluation

2021 ◽  
Vol 31 (Supplement_2) ◽  
Author(s):  
Anabela Andrade ◽  
Jorge Balteiro
Keyword(s):  
Overall Survival ◽  
Targeted Therapy ◽  
Braf Inhibitor ◽  
Progression Free Survival ◽  
Mek Inhibitor ◽  
Advanced Melanoma ◽  
New Drugs ◽  
High Rate ◽  
Free Survival ◽  
Dismal Prognosis

Abstract Background Cutaneous melanoma is an aggressive cancer that occurs in melanocytes, located in the epidermis. Historically it has a high rate of morbidity and mortality, due to the resistance and toxicity of traditional therapies. Its incidence has increased annually by 4% to 8%. Until 2011 it was still considered a devastating and almost always fatal disease in a few months. Advances in therapies have significantly improved the results of most patients with advanced melanoma, especially those with a BRAFV600 mutation, which account for almost 50% of tumors. Before the recent evolution in treatment, the prognosis and overall survival were considered very bad. The introduction of new drugs has improved progression-free survival and overall survival, as well as producing faster clinical responses. Methods Comparison of endpoints such as progression-free survival and overall melanoma survival from the Summary of Product Characteristics (SPC) studies of each drug in the therapeutic groups under assessment used in the disease. The variables used were the Endpoints Global Survival at various times (12 months, 24 months, 36 months and the median) and Progression-Free Survival. Results Combined immunotherapy (Nivolumab and Ipilimumab) improves overall survival and progression-free survival, achieving better results than targeted therapy. In this, the combination of a BRAF inhibitor and a MEK inhibitor, presents better results with the combination of Encorafenib and Binimetinib. Conclusions Both targeted therapy and immunotherapy transform melanoma with a dismal prognosis into a life-threatening illness.

Adaptive Dosing of Nivolumab + Ipilimumab Immunotherapy Based Upon Early, Interim Radiographic Assessment in Advanced Melanoma (The ADAPT-IT Study)

2021 ◽  
Author(s):  
Michael A. Postow ◽  
Debra A. Goldman ◽  
Alexander N. Shoushtari ◽  
Allison Betof Warner ◽  
Margaret K. Callahan ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Progression Free Survival ◽  
Advanced Melanoma ◽  
Computed Tomography Scan ◽  
Free Survival ◽  
Immunotherapy Trial ◽  
Grade 3 ◽  
Almost All ◽  
Tomography Scan

PURPOSE Nivolumab + ipilimumab (nivo + ipi) is highly efficacious but has high toxicity. Standard treatment in advanced melanoma is four doses of nivo + ipi followed by nivo alone. Whether four doses of nivo + ipi are needed is unclear. METHODS The Adaptively Dosed ImmunoTherapy Trial (ADAPT-IT) study ( NCT03122522 ) is a multicenter, single-arm phase II clinical trial. Patients received two doses of nivo (1 mg/kg) + ipi (3 mg/kg) followed by a computed tomography scan at week 6. Patients without new lesions or index lesion tumor growth of > 4% had protocol-defined early favorable antitumor effect (FATE) and ceased nivo + ipi, transitioning to nivo monotherapy. Patients without FATE at week 6 received the standard third and fourth doses of nivo + ipi followed by nivo monotherapy. The primary end point was response rate by RECIST 1.1 at week 12. Secondary end points included additional efficacy assessments and safety. RESULTS Sixty patients were enrolled; 41 patients (68%) had FATE at week 6 and met criteria for stopping nivo + ipi. Best overall response rates by RECIST at week 12 or any time afterward were 48% (95% CI, 35 to 62) and 58% (95% CI, 45 to 71), respectively. With a median follow-up of 25 months, the estimated 18-month progression-free survival and overall survival are 52% and 80%, respectively. Fifty seven percent of patients had grade 3-5 treatment-related toxicity. CONCLUSION The efficacy and toxicity of standard four dose nivo + ipi induction therapy in melanoma is likely driven by the first two doses. An interim computed tomography scan after two doses guided cessation of combination dosing and identified almost all responders. Longer follow-up and further study are needed to fully understand the implications of a shortened induction course of nivo + ipi.

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