TIL therapy improves PFS in patients with advanced melanoma

Tumour-infiltrating lymphocyte therapy significantly improved progression-free survival (PFS) in patients with advanced melanoma compared with standard-of-care treatment with ipilimumab, according to the M14TIL trial presented at ESMO 2022.

“This study shows for the first time in a randomized, controlled trial that cell therapy can be efficacious and beneficial for patients with solid cancers [compared with standard immunotherapy],” said lead author Dr John Haanen from the Netherlands Cancer Institute in Amsterdam, The Netherlands.

This phase III trial involved 168 patients (aged ≥18 to ≤75 years) with unresectable stage IIIC–IV melanoma. Participants were randomized to receive either TIL treatment or ipilimumab (3 mg/kg) every 3 weeks for a maximum of four doses (n=84 in each group). Patients in the TIL arm underwent metastasectomy to retrieve one or two lesions. After 4–5 weeks, they were admitted to the hospital to receive chemotherapy (cyclophosphamide 600 mg/kg/day for 2 days plus fludarabine 25 mg/m²/day for 5 days), followed by a single infusion of 5x10⁹ to 2x10¹¹ TIL and high-dose IL-2 600,000 IU/kg/dose every 8 hours for a maximum of 15 doses. [ESMO 2022, abstract LBA3]

At a median follow-up of 33 months, patients who received TIL treatment had significantly improved PFS than those who received ipilimumab (median 7.2 vs 3.1 months; hazard ratio [HR], 0.50; p<0.001).

The 6-month PFS rate was higher among those treated with TIL compared with ipilimumab (52.7 percent vs 21.4 percent).

In addition, patients treated with TIL achieved a higher overall response rate (48.8 percent vs 21.4 percent) and complete response rate (20.2 percent vs 7.1 percent) than those treated with ipilimumab.

There was also a trend toward improved overall survival (OS) among those on TIL treatment than ipilimumab (median 25.8 vs 18.9 months; HR, 0.83, 95 percent CI, 0.54–1.27; p=0.39). This was not statistically significant and the study was not powered to show an OS difference between the treatment arms, Haanen noted.

Although grade ≥3 treatment-related adverse events occurred in all patients treated with TIL, the safety profile was manageable with no new safety signals observed, Haanen said.

“[I]f patients fail first-line treatments, then the options become very scarce, particularly for patients failing anti-PD-1 drugs, so there is a real unmet need,” said Haanen. “In our study, 89 percent of the patients had failed [prior] anti-PD-1 treatment.”

The results further support the use of TIL therapy as first- or second-line treatment for patients with advanced melanoma, particularly in anti-PD-1 refractory patients, Haanen said. “TIL could become a possible new treatment option for patients with advanced melanoma”.