Immune Checkpoint Inhibitors

Prof Dr Mireille Fontsa Langouo, a medical oncologist at Institut Jules Bordet, Brussels, Belgium, provides some key insights into treating acral lentiginous melanoma (ALM). She also emphasises the emerging role of biomarkers in predicting patient response and managing risks during immune checkpoint inhibitor (ICI) therapy. 

Two studies focused on the poor response of ALM—a rare but aggressive melanoma subtype—to ICIs. Data from the EUMela Registry showed that in 160 stage III–IV ALM patients, response rates, PFS and OS were significantly lower compared to other melanoma types, likely due to the typically low mutational burden in ALM.

A second study analysed tumour immune cell infiltration in ALM across ethnic groups. It found notable variations in immune cell distribution. Tumours from Hispanic/Latino and African-American patients had higher macrophage infiltration, while non-Hispanic white patients showed more activated natural killer cells. These findings highlight the biological complexity of ALM and the need for targeted therapies and inclusive research.

The second group of studies explored potential blood-based biomarkers for monitoring treatment response and risk.

A Belgian study (Ghent University Hospital) evaluated PD-L1 and LAG-3 expression on circulating T cells in patients receiving anti-PD-1 therapy combined with stereotactic radiotherapy. In 20 patients, low PD-L1 and LAG-3 levels correlated with more durable responses after two treatment cycles, suggesting that early downregulation of these markers may predict long-term benefit.

Another large study (n > 300) investigated D-dimer levels in stage III–IV melanoma patients treated with ICIs. Elevated baseline D-dimers were associated with increased thromboembolic risk during treatment, as well as shorter PFS and OS. D-dimer measurement may, therefore, serve as a dual-purpose biomarker, identifying patients at risk of complications and predicting poorer outcomes.