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A Melanoma Patient-Derived Xenograft Model
Published on: May 20, 2019
Immune-Related Adverse Events in Patients with Melanoma Treated with B-RAF/MEK Target Therapy: Occurrence and
Alessia Capone1, Maria Luigia Carbone2,3, Simona Mastroeni4
1Molecular Neuroimmunology Laboratory, IRCCS Santa Lucia Foundation, 00179 Rome, Italy.
Background/Objectives:
BRAF and/or MEK inhibitors are widely used for patients with BRAF-mutated melanoma, but no biomarkers of response or resistance are currently available. Besides adverse events in different organs, target therapy with BRAF and/or MEK inhibitors may induce the onset of immune-related adverse events (irAEs) that have been considered as possible biomarkers of good prognosis in patients with melanoma.
Methods:
To investigate this aspect, we analyzed the occurrence of irAEs in a cohort of 158 patients treated with BRAF and MEK inhibitors. We also analyzed by flow cytometry the subsets of circulating immune cells in the patients who developed irAEs and matched controls.
Results:
We found that irAEs occurred in 3 out of 101 patients (3%) who experienced adverse events. These three patients did not exhibit any specific clinical features or circulating immune cell subtypes that could be associated with a positive response to treatment. However, the onset of toxicity in the entire patient cohort was associated with longer progression-free survival. Notably, the frequency of circulating follicular helper T cells increased in all examined patients during the first two months of treatment.
Conclusions:
The small sample size prevents us from determining whether irAEs are effectively caused by BRAF/MEK inhibitors or if they are a random event. Additionally, we cannot conclude whether irAEs are related to a better outcome. Nevertheless, we note that BRAF/MEK inhibition may alter the composition of circulating immune cells in melanoma patients. This aspect should be investigated further before proposing combinations of target therapies and immunotherapies.
Insights
Immune-related adverse events (irAEs) in melanoma patients on BRAF/MEK inhibitors were studied. While irAEs were rare and not linked to specific patient features, their onset correlated with longer progression-free survival, suggesting potential prognostic value.
Area of Science:
- Oncology
- Immunology
- Pharmacology
Background:
- BRAF and/or MEK inhibitors are standard treatments for BRAF-mutated melanoma.
- Biomarkers for treatment response and resistance to these inhibitors are lacking.
- Immune-related adverse events (irAEs) are potential indicators of prognosis in melanoma patients.
Purpose of the Study:
- To investigate the occurrence and potential prognostic value of irAEs in melanoma patients treated with BRAF and/or MEK inhibitors.
- To analyze circulating immune cell subsets in patients who developed irAEs.
- To explore the relationship between irAEs and treatment outcomes.
Main Methods:
- Analysis of irAE occurrence in a cohort of 158 patients treated with BRAF and MEK inhibitors.
- Flow cytometry analysis of circulating immune cell subsets in patients with irAEs and matched controls.
- Correlation of irAEs with clinical features, treatment response, and progression-free survival.
Main Results:
- irAEs occurred in 3% of patients experiencing adverse events.
- No specific clinical features or immune cell subtypes were associated with irAEs and positive treatment response.
- The onset of toxicity was associated with longer progression-free survival in the cohort.
- Circulating follicular helper T cell frequency increased in all patients during the initial two months of treatment.
Conclusions:
- The small sample size limits definitive conclusions on irAE causality and prognostic significance.
- BRAF/MEK inhibition may alter circulating immune cell composition in melanoma patients.
- Further research is needed to clarify the role of irAEs and immune cell changes before combining targeted therapies with immunotherapies.
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