Advanced melanoma: Tumour-infiltrating lymphocytes outperform ipilimumab

Second-line treatment with TIL improves PFS compared with ipilimumab in patients with advanced, non-resectable stage III–IV melanoma.

Great unmet need for novel treatments in advanced melanoma

Although immune checkpoint inhibitors and targeted therapies have profoundly improved outcome of patients with (advanced) melanoma, approximately 50% of patients still die from their disease within 5 years following diagnosis of stage IV disease1. Thus, there is a great unmet need for novel treatment options in this patient population.

Adoptive cell therapy with TIL is a (elaborative and time-consuming) treatment modality with promising response rates of 36–70% in heavily pre-treated patients with advanced melanoma, observed in multiple phase 1/2 trials2,3. Dr John Haanen (Netherlands Cancer Institute, the Netherlands) and colleagues performed the first investigator-driven, open-label, randomised-controlled, phase 3 clinical trial (NCT02278887) comparing treatments with TIL and ipilimumab4.

In the trial, 168 patients with unresectable, stage III–IV cutaneous melanoma who had progression after 1 line of systemic treatment (no ipilimumab) were randomised to receive TIL treatment (single infusion of ≥5x109 TILs) or ipilimumab (3 mg/kg every 3 weeks, max. 4 doses). About 90% of the patients had received prior anti-PD1 therapy. Primary endpoint of study was PFS in the intention-to-treat (ITT) population; secondary endpoints were overall and complete response rate (RR), overall survival (OS), and safety.

OS data is immature, but the trend favours TIL

The trial met its endpoint: with a median follow-up of 33 months, median PFS was 7.2 months for the patients randomised to TIL treatment versus 2.1 months for the patients treated with ipilimumab (HR 0.50; P<0.001). PFS rates at 6 months were 52.7% and 21.4%, respectively. TIL therapy was superior to ipilimumab in all pre-specified subgroups. ORR was 48.8% in the TIL-treated patients (20.2% complete response) versus 21.4% in the ipilimumab-treated patients (7.1% complete response).

Immature OS data showed a trend in favour of TIL treatment; median OS was 25.8 months in the TIL-treated patients versus 18.9 months in the ipilimumab-treated patients (HR 0.83; P=0.39). Safety of TIL treatment was manageable and scores for health-related quality-of-life were significantly higher in TIL-treated patients during the 60 months of follow-up (mean difference at 6 months: 7.7; P<0.01).

“This first randomised phase 3 trial demonstrates that second-line TIL significantly improves PFS compared with ipilimumab in patients with unresectable, advanced melanoma. Therefore, TIL could become a possible new treatment option for this population,” Dr Haanen concluded.

  1. Larkin J, et al. N Engl J Med 2019;381:1535–1546.
  2. Van den Berg JH, et al. J Immunother Cancer. 2020;8:e000848.
  3. Sarnaik AA, et al. J Clin Oncol. 2021;39:2656–2666.
  4. Haanen JBAG, et al. Treatment with tumor-infiltrating lymphocytes (TIL) versus ipilimumab for advanced melanoma: Results from a multicenter, randomized phase III trial. Abstract LBA3, ESMO Congress 2022, Paris, France, 09–13 September.