Predictive Impact of Tumor Mutational Burden on Real-World Outcomes of First-Line Immune Checkpoint Inhibition in Metastatic Melanoma
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View abstract on PubMed
Summary
This summary is machine-generated.High tumor mutational burden (TMB) predicts better outcomes for metastatic melanoma patients on immune checkpoint inhibitors (ICI). Combining TMB and BRAF status can help choose the best first-line ICI therapy.
Area Of Science
- Oncology
- Genomics
- Immunotherapy
Background
- Metastatic melanoma treatment has advanced with immune checkpoint inhibitors (ICIs).
- Tumor mutational burden (TMB) is a potential biomarker for predicting ICI response.
- Optimal TMB thresholds and reliability in real-world settings for first-line therapy remain unclear.
Purpose Of The Study
- To evaluate the predictive value of high TMB (TMB-H) for outcomes in metastatic melanoma patients receiving first-line ICI therapy.
- To assess the reliability of TMB thresholds in guiding treatment selection in a real-world cohort.
- To investigate the interplay between TMB, BRAF status, and ICI regimen choice.
Main Methods
- A real-world cohort of 497 metastatic melanoma patients receiving first-line anti-PD-1 or dual anti-PD-1/anti-CTLA-4 ICI was analyzed.
- Patients underwent comprehensive genomic profiling for TMB assessment.
- Outcomes, including progression-free survival and overall survival, were compared between TMB-high (≥10 muts/Mb) and TMB-low (<10 muts/Mb) groups.
Main Results
- TMB-high status independently predicted superior progression-free and overall survival across both monotherapy and dual ICI treatments.
- Dual ICI did not offer significant advantage in BRAF wild-type patients.
- The greatest benefit from dual ICI was observed in the TMB 10-19 muts/Mb group, while TMB-very high (≥20 muts/Mb) BRAF-mutant patients may benefit more from monotherapy.
Conclusions
- High TMB is a reliable predictor of superior outcomes in patients with metastatic melanoma treated with first-line ICIs.
- Coassessment of BRAF status and TMB can inform optimal first-line ICI regimen selection.
- These findings support the use of TMB as a biomarker to personalize melanoma treatment strategies.
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