Tumor-Infiltrating Lymphocytes Outperform Ipilimumab in Advanced Melanoma

Personalized treatment using tumor-infiltrating lymphocytes (TILs) can improve progression-free survival (PFS), when compared with ipilimumab, in patients with advanced melanoma, according to phase 3 results presented at ESMO Congress 2022.¹

“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,” study presenter John B.A.G. Haanen, MD, PhD, of the Netherlands Cancer Institute in Amsterdam, said in a statement.²

The phase 3 trial (ClinicalTrials.gov Identifier: NCT02278887) included 168 adults who had unresectable stage IIIC-IV melanoma that had progressed after 1 line of systemic treatment, not including ipilimumab.¹ The patients were randomly assigned to receive TILs (n=84) or ipilimumab (n=84).

The TILs were created using a melanoma lesion surgically removed from the patient. The cells were expanded ex vivo via the addition of interleukin-2 (IL-2), anti-CD3, and feeder cells.

Patients given TILs received nonmyeloablative, lymphodepleting chemotherapy before receiving a single infusion of TILs (5×10⁹ to 2×10¹¹) and high-dose IL-2. Ipilimumab was administered at a dose of 3 mg/kg, given every 3 weeks, for a maximum of 4 doses.

At baseline, more than 80% of patients in either arm had a World Health Organization performance status of 0, more than 85% had previously received anti-PD-1 therapy, and more than half were men. The median age was 59 (range, 26-74) years in the TIL arm and 58 (range, 30-77) years in the ipilimumab arm.

The median follow-up was 33.5 months in the TIL arm and 33.0 months in the ipilimumab arm. The median PFS was 7.2 months in the TIL arm and 3.1 months in the ipilimumab arm (hazard ratio [HR], 0.50; 95% CI, 0.35-0.72; P <.001). The 6-month PFS rates were 52.7% and 21.4%, respectively.

The overall response rate was 48.8% in the TIL arm and 21.4% in the ipilimumab arm. The complete response rates were 20.2% and 7.1%, respectively.

The median overall survival was 25.8 months in the TIL arm and 18.9 months in the ipilimumab arm (HR, 0.83; 95% CI, 0.54-1.27; P =.39). The 2-year overall survival rates were 54.3% and 44.1%, respectively.

Grade 3 or higher treatment-related adverse events (TRAEs) occurred in 57.3% of patients in the ipilimumab arm. Grade 3 or higher TRAEs linked to lymphodepleting chemotherapy were reported in 100% of patients who received it.

Grade 3 or higher TRAEs linked to the TILs plus IL-2 occurred in 96.3% of patients who received the treatment. The most common of these events were febrile neutropenia (72.5%), hypophosphatemia (60.0%), fever (45.0%), and dyspnea (18.8%).

Based on these findings, Dr Haanen concluded that TILs may represent a new treatment option for patients with advanced melanoma.

Disclosures: Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original references for a full list of disclosures.

References

1. Haanen JBAG, Rohaan M, Borch TH et al. Treatment with tumor-infiltrating lymphocytes (TIL) versus ipilimumab for advanced melanoma: Results from a multicenter, randomized phase III trial. Presented at ESMO 2022; September 9-13, 2022. Abstract LBA3.
2. Cell therapy improves progression-free survival in advanced melanoma, first phase 3 study shows. ESMO. News release. Published September 10, 2022.