Dutch researchers report doubled survival benefits with tumour-infiltrating lymphocytes (TILs) versus standard of care therapy (ipilimumab) in patients with metastatic melanoma. This is the first phase-III study demonstrating the clinical benefits of TILs for solid tumours in metastatic settings. These findings were recently presented at the ESMO congress.
Earlier studies have reported the efficacy of TILs in treating cancers, mainly in phase 1 and 2 trials. The researchers from Leiden University and the Netherlands Cancer Institute, Amsterdam, decided to initiate a phase-III trial to determine if TILs could become the new standard of care.
The phase-III, multicentre, randomised, open-label study enrolled 168 unresectable stage III-IV melanoma patients. All the participants were randomly assigned to receive either a single infusion of TILs (n=84) or up to four doses of ipilimumab (n=84). Despite treatment with first-line or adjuvant-PD-1 therapy, most (>80%) patients experienced disease progression. Further, all patients receiving TILs underwent preconditioning lymphodepletion before TIL infusion and later were administered higher=dose interleukin-2 to promote TIL activity. The study’s primary endpoint was progression-free survival (Pwith) in the intent to treat the population, whereas the secondary endpoints included overall response rate (ORR), complete response rate (CRR), overall survival (OS) and safety.
The median PFS was significantly extended in patients who received TILs (7.2 vs 3.1 months; HR = 0.5; 95% CI, 0.35-0.72) than those in the ipilimumab group. Importantly, the six-month PFS rates were doubled with TILs (52.7%) compared to ipilimumab (21.4%). TIL treatment also improved ORR (48.8% vs. 21.4%), CRR (20.2% vs. 7.1%) along with improving clinical benefits (67.9% vs. 39.3%). Further, the OS was also extended in the TIL arm compared to the ipilimumab arm (25.8 vs 18.9 months, HR = 0.83; 95% CI, 0.54-1.27). Notably, all the patients in TIL group experienced grade 3 or above adverse events compared to 57.3% of those in the ipilimumab group.
The phase-III study demonstrates the clinical efficacy of TIL therapy for advanced melanoma patients. It is likely to become the standard of care for metastatic melanomas refractory to immune checkpoint inhibitors.