Real-World Data Support Clinical Benefit With Lifileucel in Previously Treated Advanced Melanoma

Patients with previously treated advanced melanoma derived clinical benefit with lifileucel (Amtagvi) in a real-world setting, according to findings presented at the 2026 Transplantation & Cellular Therapy Meetings. Among 41 treated patients, the overall response rate was 44%, with higher response rates observed in patients who had received fewer prior lines of therapy.

“Lifileucel demonstrated meaningful real-world clinical activity in patients with advanced melanoma. Higher response rates were observed in patients with lower disease burden and fewer planned prior lines of therapy, supporting earlier referral to lifileucel,” stated Lilit Karapetyan, MD, MS, assistant member in the department of cutaneous oncology at Moffitt Cancer Center and assistant professor at the University of South Florida Morsani College of Medicine, in her presentation of the data.

Study Design and Patient Characteristics

The study evaluated 41 adult patients with advanced melanoma who received lifileucel at 4 treatment centers in the US. The treatment protocol involved a standardized lymphodepletion regimen of cyclophosphamide and fludarabine, followed by a single lifileucel infusion and up to 6 doses of high-dose interleukin-2 (IL-2).

The patient cohort reflected a high-risk population often underrepresented in strict clinical trials. The median age was 59 years (range, 28–79). Cutaneous melanoma was the most common subtype included at 71%, whereas 17% had mucosal melanoma, and 10% had acral melanoma. Baseline metastases were present in the liver in 32% and in the brain in 29% of patients.

Patients had received a median of 3 prior systemic anticancer therapies (range, 1–7) including adjuvant or neoadjuvant treatment. Median time from tumor harvest to lymphodepletion initiation was 44 days.

Notably, 44% required bridging therapy while awaiting lifileucel manufacturing. According to Karapetyan, bridging therapy largely consisted of patients with BRAF or other mutations continuing prior tyrosine kinase inhibitor therapy rather than being given chemotherapy or other new treatment.

Initial Efficacy in the Real-World Setting

The primary end point was physician-assessed ORR. In this real-world cohort, the ORR was 44% (n = 18), consisting of 16 partial responses (39%) and 2 complete responses (5%). This exceeds the 31.5% ORR observed in the C-144-01 registrational trial (NCT02360579) that led to lifileucel’s approval.²

Notably, in 23 patients treated with 2 or fewer prior lines of systemic therapy, there was a higher ORR of 52%, but in 18 patients who had 3 or more prior lines, the ORR was 33%.¹ Response rates were also higher in those patients with stage M1a disease vs M1b/c/d (63% vs 39%, respectively). Response rates were 50% and 57% in acral and mucosal subtypes compared with 38% in cutaneous subtypes, which Karapetyan highlighted as favorable for these 2 subtypes that do not respond well to immune checkpoint inhibition.

Patients who did not require bridging therapy between tumor procurement and lymphodepletion had a higher ORR of 61% compared with 22% in those who needed bridging.

Regarding the surgical resection needed to produce the TIL product, Karapetyan said, “It was notable that responses were observed across several harvest sites, including liver, lymph nodes, acute soft tissues, and there was no difference with the total number of infused cells.

“In terms of tumor harvest site, they were very similar, with the range of 11 to 50 billion [cells], and no significant difference was observed with [in-specification] product for total number of cells infused between responders and non-responders,” she added.

Preliminary progression-free survival (PFS) and overall survival (OS) were reported at 6 months’ follow-up. The median PFS and OS were 4.4 months and 10.2 months, respectively. In those with 2 or fewer prior lines, median PFS was 5.4 months and OS was not reached, whereas in those with 3 or more lines, median PFS was 3.1 months and OS was 10.2 months. Karapetyan noted that high lactate dehydrogenase was associated with poorer PFS as well as lower ORR.

IL-2 Use and Safety

Patients received a median of 5 of a maximum 6 IL-2 doses. Reasons for discontinuation of IL-2 primarily included “cardiovascular disorders such as hypertension, tachycardia, followed by intolerable fever, rigors, renal disorders, infections, hypoxia, hyponatremia, transaminitis, as well as patient refusal,” with many patients having mixed reasons, according to Karapetyan. Notably, patients who received 3 or fewer doses of IL-2 had a 58% ORR whereas those who had 4 or more doses had an ORR of 38%.

Patients were hospitalized for a median of 13 days (range, 4–50). One patient had interruption of cyclophosphamide and 3 had interruption of fludarabine. There were no deaths within 45 days of TIL infusion.

Study Limitations and Conclusions

A key limitation of retrospective reporting on outcomes with lifileucel is the bias toward patients who were able to receive TILs vs those who were referred but did not receive therapy. This question was posed to Karapetyan after her presentation by Richard Maziarz, MD, of Oregon Health and Science University, who brought up that an intent-to-treat approach would demonstrate this issue. In a single-center study using this approach that his institution presented in a poster at the conference, less than a third of TIL therapy referrals proceeded to TIL infusion.³

Karapetyan said that this is an issue that varies widely across treatment centers. Many centers do not treat high-risk patients because they may not benefit and will have significant toxicities. She also noted that an upcoming publication from the Society of Surgical Oncologists will include data on manufacturing problems and out-of-specification TIL products.

“The message is that if you send patients earlier, if they have [fewer] lines of therapy, they have lower burden of a disease. They are more functional. This is the right time that they need to receive lifileucel,” Karapetyan concluded.

References

1. Karapetyan L, Moser J, Ma BT, et al. Real-world, evidence-based, retrospective study of patients infused with commercially released lifileucel for unresectable or metastatic melanoma. Presented at: 2026 Transplantation & Cellular Therapy Meetings. February 4-7, 2026. Salt Lake City, Utah. Abstract 48.
2. Sarnaik AA, Hamid O, Khushalani NI, et al. Lifileucel, a tumor-infiltrating lymphocyte therapy, in metastatic melanoma. J Clin Oncol. 2021;39(24):2656-2666. doi:10.1200/JCO.21.00612
3. Desai A, Valenzuela C, Blackburn M, et al. Real world outcomes of a single-center tumor infiltrating lymphocyte (TIL) melanoma therapy program with commercial lifileucel. Presented at: 2026 Transplantation & Cellular Therapy Meetings. February 4-7, 2026. Salt Lake City, Utah. Poster 231.