scholarly journals Thinking Small: Small Molecules as Potential Synergistic Adjuncts to Checkpoint Inhibition in Melanoma

2021 ◽  
Vol 22 (6) ◽  
pp. 3228
Author(s):  
Alexander C. Chacon ◽  
Alexa D. Melucci ◽  
Shuyang S. Qin ◽  
Peter A. Prieto
Keyword(s):  
Skin Cancer ◽  
Small Molecules ◽  
Metastatic Melanoma ◽  
Immune Checkpoint ◽  
Treatment Resistance ◽  
Checkpoint Inhibition ◽  
Immune Checkpoint Inhibition ◽  
Specific Effector ◽  
Melanoma Treatment ◽  
Therapeutic Responses

Metastatic melanoma remains the deadliest form of skin cancer. Immune checkpoint inhibition (ICI) immunotherapy has defined a new age in melanoma treatment, but responses remain inconsistent and some patients develop treatment resistance. The myriad of newly developed small molecular (SM) inhibitors of specific effector targets now affords a plethora of opportunities to increase therapeutic responses, even in resistant melanoma. In this review, we will discuss the multitude of SM classes currently under investigation, current and prospective clinical combinations of ICI and SM therapies, and their potential for synergism in melanoma eradication based on established mechanisms of immunotherapy resistance.

scholarly journals Response and survival of metastatic melanoma patients treated with immune checkpoint inhibition for recurrent disease on adjuvant dendritic cell vaccination

2020 ◽  
Vol 9 (1) ◽  
pp. 1738814
Author(s):  
Wouter W. van Willigen ◽  
Martine Bloemendal ◽  
Marye J. Boers-Sonderen ◽  
Jan Willem B. de Groot ◽  
Rutger H.T. Koornstra ◽  
...  
Keyword(s):  
Dendritic Cell ◽  
Metastatic Melanoma ◽  
Immune Checkpoint ◽  
Recurrent Disease ◽  
Dendritic Cell Vaccination ◽  
Checkpoint Inhibition ◽  
Immune Checkpoint Inhibition ◽  
Melanoma Patients

scholarly journals 489 Investigation of the immune infiltrate of metastatic melanoma under immune checkpoint inhibition

2016 ◽  
Vol 136 (9) ◽  
pp. S244
Author(s):  
J.C. Hassel ◽  
M. Flossdorf ◽  
S. Hänzelmann ◽  
J. Winkler ◽  
L. Appel ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
Immune Checkpoint ◽  
Checkpoint Inhibition ◽  
Immune Checkpoint Inhibition ◽  
Immune Infiltrate

Delta-radiomics for prediction of pseudoprogression in malignant melanoma treated with immune checkpoint inhibition.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 9575-9575 ◽  
Author(s):  
Lucas Basler ◽  
Hubert Gabrys ◽  
Sabrina A. Hogan ◽  
Marta Bogowicz ◽  
Diem Vuong ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
Immune Checkpoint ◽  
Prediction Models ◽  
Lung Metastases ◽  
Univariate Analysis ◽  
Response Rates ◽  
Checkpoint Inhibition ◽  
Immune Checkpoint Inhibition ◽  
Melanoma Patients

9575 Background: Distinguishing progressive disease (PD) from pseudoprogression (PP) in patients treated with immune-checkpoint inhibition (ICI) is challenging and usually requires confirmation follow-up imaging or invasive diagnostic techniques. This project aimed to identify predictive radiomic signatures for PP from CT imaging. Methods: The response to ICI of 105 metastatic melanoma patients with 645 metastases was retrospectively correlated with radiomic signatures (172 total features). All metastatic lesions were delineated at 3 time points: prior to ICI (t0), at 3 (t1) and 6 months (t2). Response was defined individually for each metastasis using RECIST 1.1, comparing baseline t0 to t2. Three prediction models for PP were built: CT radiomics at t0 and t1, as well as the relative difference between both t0 and t1 (delta-radiomics). Results: Median follow-up was 18 months and 2-year OS and PFS were 72% and 25%, respectively. Median OS: not reached, median PFS: 6 months. Response per lesion at t1: 13% complete remission (CR), 19% partial remission (PR), 52% stable disease (SD) and 16% PD. At t2: 16% CR, 31% PR, 38% SD and 15% PD. 106 progressive lesions were identified at t1, of which, 26 changed to SD, 1 to CR and 3 to PR at t2, resulting in 30 PPs (4.7%). Metastasis location significantly influenced response rates but was not associated with PP (p = 0.4). Lung metastases had significantly higher response rates than soft tissue (p < 0.001), liver (p < 0.001) and bone metastases (p = 0.008). Univariate analysis followed by removal of correlated features revealed no significant radiomic features associated with PP at t0. One independent feature was identified at t1 (AUC 0.74), while delta-radiomics was the best performing approach, identifying four independent features (AUC 0.72 to 0.81). A final multivariate delta radiomics logistic regression model was generated and internally validated, achieving an AUC of 0.81 (± 0.11, 10-fold cross-validation). Conclusions: Metastasis location significantly influenced response rates and CT-based delta-radiomics is a promising biomarker for early differentiation between pseudoprogression and true progression in metastatic melanoma patients treated with ICI.

scholarly journals Sex-Based Differences in Treatment with Immune Checkpoint Inhibition and Targeted Therapy for Advanced Melanoma: A Nationwide Cohort Study

Cancers ◽  
2021 ◽  
Vol 13 (18) ◽  
pp. 4639
Author(s):  
Monique van der Kooij ◽  
Olaf Dekkers ◽  
Maureen Aarts ◽  
Franchette van den Berkmortel ◽  
Marye Boers-Sonderen ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Advanced Melanoma ◽  
Checkpoint Inhibition ◽  
Immune Checkpoint Inhibition ◽  
Survival Difference ◽  
Melanoma Treatment ◽  
Melanoma Patients ◽  
Treatment Responses ◽  
Grade 3 ◽  
Meta Analyses

Recent meta-analyses show conflicting data on sex-dependent benefit following systemic treatment for advanced melanoma patients. We examined the nationwide Dutch Melanoma Treatment Registry (July 2013–July 2018), assessing sex-dependent differences in advanced melanoma patients (stage IIIC/IV) with respect to clinical characteristics, mutational profiles, treatments initiated, grade 3–4 adverse events (AEs), treatment responses, and mortality. We included 3985 patients, 2363 men (59%) and showed that although men and women with advanced melanoma differ in clinical and tumor characteristics, the safety profile of immune checkpoint inhibition (ICI) is comparable. The data suggest a 10% survival advantage for women, mainly seen in patients ≥60 years of age and patients with BRAF V600 mutant melanoma. Following ICI there was no survival difference.

Cutaneous autoimmune effects in the setting of therapeutic immune checkpoint inhibition for metastatic melanoma

2016 ◽  
Vol 43 (9) ◽  
pp. 787-791 ◽  
Author(s):  
Mark C. Mochel ◽  
Michael E. Ming ◽  
Sotonye Imadojemu ◽  
Tara C. Gangadhar ◽  
Lynn M. Schuchter ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
Immune Checkpoint ◽  
Checkpoint Inhibition ◽  
Immune Checkpoint Inhibition

scholarly journals Immune checkpoint inhibition therapy for advanced skin cancer in patients with concomitant hematological malignancy: a retrospective multicenter DeCOG study of 84 patients

2020 ◽  
Vol 8 (2) ◽  
pp. e000897 ◽  
Author(s):  
Ulrike Leiter ◽  
Carmen Loquai ◽  
Lydia Reinhardt ◽  
David Rafei-Shamsabadi ◽  
Ralf Gutzmer ◽  
...  
Keyword(s):  
Treatment Outcome ◽  
Skin Cancer ◽  
Cell Carcinoma ◽  
Immune Checkpoint ◽  
Treatment Efficacy ◽  
Hematological Malignancy ◽  
Objective Response ◽  
Therapy Outcome ◽  
Checkpoint Inhibition ◽  
Immune Checkpoint Inhibition

BackgroundSkin cancers are known for their strong immunogenicity, which may contribute to a high treatment efficacy of immune checkpoint inhibition (ICI). However, a considerable proportion of patients with skin cancer is immuno-compromised by concomitant diseases. Due to their previous exclusion from clinical trials, the ICI treatment efficacy is poorly investigated in these patients. The present study analyzed the ICI treatment outcome in advanced patients with skin cancer with a concomitant hematological malignancy.MethodsThis retrospective multicenter study included patients who were treated with ICI for locally advanced or metastatic melanoma (MM), cutaneous squamous cell carcinoma (cSCC), or Merkel cell carcinoma (MCC), and had a previous diagnosis of a hematological malignancy irrespective of disease activity or need of therapy at ICI treatment start. Comparator patient cohorts without concomitant hematological malignancy were extracted from the prospective multicenter skin cancer registry ADOREG. Treatment outcome was measured as best overall response, progression-free (PFS), and overall survival (OS).Results84 patients (MM, n=52; cSCC, n=15; MCC, n=17) with concomitant hematological malignancy were identified at 20 skin cancer centers. The most frequent concomitant hematological malignancies were non-Hodgkin’s lymphoma (n=70), with chronic lymphocytic leukemia (n=32) being the largest entity. While 9 patients received ICI in an adjuvant setting, 75 patients were treated for advanced non-resectable disease (55 anti-PD-1; 8 anti-PD-L1; 5 anti-CTLA-4; 7 combinations). In the latter 75 patients, best objective response (complete response+partial response) was 28.0%, disease stabilization was 25.3%, and 38.6% showed progressive disease (PD). Subdivided by skin cancer entity, best objective response was 31.1% (MM), 26.7% (cSCC), and 18.8% (MCC). Median PFS was 8.4 months (MM), 4.0 months (cSCC), and 5.7 months (MCC). 1-year OS rates were 78.4% (MM), 65.8% (cSCC), and 47.4% (MCC). Comparison with respective ADOREG patient cohorts without hematological malignancy (n=392) revealed no relevant differences in ICI therapy outcome for MM and MCC, but a significantly reduced PFS for cSCC (p=0.002).ConclusionsICI therapy showed efficacy in advanced patients with skin cancer with a concomitant hematological malignancy. Compared with patients without hematological malignancy, the observed ICI therapy outcome was impaired in cSCC, but not in MM or MCC patients.

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