Changes in mucosa‑associated lymphoid tissue 1 predicts therapeutic response and survival in patients with advanced melanoma receiving programmed cell death‑1 inhibitor monotherapy

Advanced melanoma is an aggressive and dangerous form of skin cancer, and programmed cell death‑1 (PD‑1) inhibitors are recommended treatment options for patients with advanced melanoma. Mucosa‑associated lymphoid tissue 1 (MALT1) impairs CD8⁺ T‑cell activation to induce immune escape, leading to a reduction in the antitumor effect of PD‑1 inhibitors. The present study aimed to assess the prognostic implication of MALT1 in patients with advanced melanoma receiving PD‑1 inhibitor monotherapy. Blood MALT1 levels were assessed using reverse transcription‑quantitative PCR in 20 healthy controls (HCs) after enrollment and in 49 patients with advanced melanoma before (T₀), as well as 2 months (T₁) and 4 months after (T₂) PD‑1 inhibitor monotherapy. The maximum level of MALT1 in HCs (3.100) was used as the cut‑off in patients with advanced melanoma. MALT1 levels at T₀ were significantly increased in patients with advanced melanoma compared with in HCs (P<0.001). In patients with advanced melanoma, MALT1 was significantly decreased from T₀ to T₂ (P<0.001). Objective response rate (ORR) and disease control rate (DCR) were 28.6 and 59.2%, respectively. MALT1 levels at T₁ were significantly negatively associated with overall therapeutic response (P=0.001), ORR (P=0.009) and DCR (P=0.004). MALT1 levels at T₂ were significantly inversely associated with overall therapeutic response (P=0.021) and ORR (P=0.036). Moreover, MALT1 levels >3.100 at T₀ (P=0.027) and T₁ (P=0.045) were significantly associated with shorter progression‑free survival (PFS), and MALT1 levels >3.100 at T₁ were significantly associated with a poor overall survival (OS; P=0.022). Multivariate Cox regression analysis demonstrated that MALT1 levels at T0 (>3.100 vs. ≤3.100) were significantly associated with a poor PFS [hazard ratio (HR)=2.248; P=0.037], and MALT1 levels at T1 (>3.100 vs. ≤3.100) were significantly associated with a poor OS (HR=4.332; P=0.007). In conclusion, MALT1 levels are reduced following PD‑1 treatment, and a high MALT1 level is associated with a poor therapeutic response and shorter survival in patients with advanced melanoma receiving PD‑1 inhibitor monotherapy.