Lifileucel produced durable responses in heavily pretreated patients with advanced melanoma, according to study results published in the Journal of Clinical Oncology.

Researchers evaluated the efficacy and safety of lifileucel, an autologous tumor-infiltrating lymphocyte (TIL) product, in patients with advanced melanoma who had progressed on immune checkpoint inhibitors (ICIs) and targeted therapies.

Patients were enrolled from April 2017 to January 2019 at 26 sites in the phase 2, open-label study ( identifier: NCT02360579).

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The patients received cyclophosphamide (60 mg/kg) once daily for 2 days followed by fludarabine (25 mg/m2) once daily for 5 days. They then received a single infusion of lifileucel (1 × 109 – 150 × 109 cells), which was thawed and administered about 24 hours after the last dose of fludarabine. A short course of bolus interleukin-2 (IL-2; 600,000 IU/kg) was infused every 8 to 12 hours for up to 6 doses, beginning within 3 to 24 hours after patients completed the lifileucel infusion.

A total of 66 patients received a lifileucel infusion of more than 1 × 109 but less than 150 × 109 TIL cells. The patients’ median age was 55 years (range, 20-79 years), 59% were men, and 86% had stage IV melanoma at study entry.  

The patients had received a mean 3.3 prior lines of therapy (range, 1-9). All had previously received anti–programmed cell death protein 1 (anti–PD-1) or anti–programmed death ligand 1 (anti–PD-L1) therapy, and 53 (80%) had previously received anti–cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) therapy. A total of 17 patients were BRAF V600 mutation-positive, of whom 88% had received BRAF inhibitors, with or without MEK inhibitors.

At the data cutoff on April 23, 2020, the median follow-up was 18.7 months (range, 0.2-34.1 months). The study’s primary endpoint was investigator-assessed objective response rate (ORR).

The ORR was 36%, with 2 patients achieving a complete response and 22 having a partial response. An additional 29 patients had stable disease, so the disease control rate was 80%. The median duration of response had not been reached at the end of follow-up.

Among 42 patients who were primary refractory to anti–PD-1/PD-L1 therapy, the ORR was 41%, and the disease control rate was 81%. There were 2 complete responses, 15 partial responses, 17 patients with stable disease, 5 with progressive disease, and 3 patients who were nonevaluable. The median duration of response was not reached in this subpopulation.

All patients had at least 1 treatment-emergent adverse event (TEAE). The most frequently occurring grade 3/4 TEAEs were thrombocytopenia (82%), anemia (56%), febrile neutropenia (55%), neutropenia (39%), hypophosphatemia (35%), leukopenia (35%), and lymphopenia (32%).

Fatal TEAEs occurred in 2 patients. One was due to intra-abdominal tumor hemorrhage reported as possibly related to TILs, and the other was due to acute respiratory failure assessed as not related to TILs. The incidence of TEAEs decreased rapidly over time, according to the study authors.

They concluded that lifileucel “represents a potential new standard of care for patients with advanced melanoma following failure of ICI and targeted therapy.”

“Patients with advanced melanoma who have failed anti–PD-1 therapy (and BRAF ± MEK inhibitors if BRAF V600 mutation positive), irrespective of baseline tumor characteristics, should be considered for the one-time lifileucel therapy as second-line therapy (third-line if BRAF V600 mutation positive) if they have performance status and organ function adequate for administration of lymphodepleting chemotherapy and a shortened course of IL-2,” the authors added.

Disclosures: This research was supported by Iovance Biotherapeutics Inc. Several study authors declared affiliations with the pharmaceutical and medical device industries. Please see the original reference for a full list of authors’ disclosures.


Sarnaik AA, Hamid O, Khushalani NI, et al. Lifileucel, a tumor-infiltrating lymphocyte therapy, in metastatic melanoma. J Clin Oncol. Published online May 12, 2021. doi:10.1200/JCO.21.00612