Treatment with tumour-infiltrating lymphocytes for advanced melanoma outperforms ipilimumab

Second-line treatment with tumour-infiltrating lymphocytes (TIL) improved progression-free survival (PFS) compared with ipilimumab in patients with advanced, non-resectable stage III–IV melanoma, the results from an investigator-driven randomised phase 3 trial showed.

Although immune checkpoint inhibitors and targeted therapies have profoundly improved the outcome of patients with (advanced) melanoma, approximately 50% of patients still die from their disease within 5 years following diagnosis of stage IV disease [1]. Adoptive cell therapy with TIL is an (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 trials [2,3]. Prof. 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 ipilimumab [4].

In this 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 ≥5×10⁹ TILs) or ipilimumab (3 mg/kg every 3 weeks, max. 4 doses). About 90% of the participants had received prior anti-PD1 therapy. The primary endpoint of the study was PFS in the intention-to-treat (ITT) population; secondary endpoints were overall and complete response rate (RR), overall survival (OS), and safety.

The trial met its endpoint: with a median follow-up of 33 months, the median PFS was 7.2 months for the participants 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% (TIL vs ipilimumab, respectively). ORR was 48.8% in the TIL-receiving participants (20.2% complete response) compared with 21.4% in the ipilimumab-treated participants (7.1% complete response). Preliminary OS data showed a trend in favour of TIL treatment; the median OS was 25.8 months in the TIL-receiving participants versus 18.9 months in participants on ipilimumab (HR 0.83; P=0.39). The safety of TIL treatment was manageable and scores for health-related quality-of-life were significantly higher in TIL-treated participants during the 60 months of follow-up (Δ_{mean at 6 months} 7.7; P<0.01) than in the ipilimumab-treated group.

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

1. Larkin J, et al. N Engl J Med. 2019;381(16):1535–1546.
2. Van den Berg JH, et al. J Immunother Cancer. 2020;8(2):e000848.
3. Sarnaik AA, et al. J Clin Oncol. 2021;39(24):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, 09–13 September, Paris, France.

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Posted on 16 November 20228 February 2024