Considering Lifileucel Use in Patients With Brain-Metastatic Melanoma

Lifileucel (Amtagvi) is an approved tumor-infiltrating lymphocyte (TIL) therapy for patients with advanced melanoma, but there are limited data on treatment of patients with brain metastases. During a live Case-Based Roundtable event in Cleveland, Ohio, Daniel Olson, MD, assistant professor of medicine at UChicago Medicine, discussed a patient case that delved into this issue and also evaluated a pilot trial that showed efficacy and tolerability in a small number of patients with brain metastases. Olson and the participants considered whether to treat lesions locally before TIL and how disease volume and timing could affect the decision.

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This is part 2 of 2 articles based on this event.

CASE SUMMARY

A 42-year-old man initially diagnosed 5 years ago with pT3aN0 cutaneous melanoma of the right calf underwent wide excision and sentinel lymph node biopsy.

• Developed multiple pulmonary lesions seen on chest imaging done for persistent cough​
• Genetic testing revealed BRAF wild-type​
• First-line: nivolumab (Opdivo) + ipilimumab​ (Yervoy)
• Achieved a partial response in the lungs but discontinued after 4 cycles due to immune-related colitis ​
• Presents today with headaches and intermittent nausea​
• Brain MRI reveals 3 small lesions in the frontal lobe​
• Pulmonary lesions stable​
• ECOG performance status of 0​
• Normal lactate dehydrogenase levels

Targeted Oncology: How would you approach treating this patient?

Daniel Olson, MD: This is somebody who has active brain metastases after progressing on ipilimumab/nivolumab and doesn't have a targeted therapy. Would you do stereotactic radiosurgery [SRS]? Would you do ipilimumab/nivolumab again, nivolumab/relatlimab [Opdualag], chemotherapy, PD-1–targeted agent, lifileucel, or other?

I think we've got a debate on that between SRS and lifileucel. I think if we went by the book here, we'd say we do probably SRS to try and stabilize them. I think typically we think about SRS if we have time. There is the consideration that if patient has really low-volume asymptomatic brain metastases and you're going to do TIL therapy, and you have time to treat them, then watch them through assessment. It's reasonable; you probably entertain some risk with the bleed. That's where you'd be talking to the treating team about platelet thresholds, and probably transfusion of patients when there are 50,000 platelets uL or something like that.

The standard right now would probably not be lifileucel, but it would be SRS and then lifileucel most likely in those patients. But again, there's a judgment call on when to introduce it if it's really small and low-volume brain metastases.

What data support the use of TILs in patients with brain metastases?

There is an ongoing trial [NCT05640193] of using lifileucel in brain metastases.¹ This is being run at Memorial Sloan Kettering Cancer Center, where they're essentially taking the patient we just described [with] asymptomatic brain metastases who also have extracranial disease that can be used for TIL procurement and then treating those patients with lifileucel. As you'd expect these patients are pretreated, have brain metastases, and they've only got efficacy in 8 patients so far, but there have been responses, stable disease, and progressive disease [n = 2 for each]. Then, looking at the adverse events, fortunately, I do not see hemorrhage here. That would be the one you worry about. , but they look pretty similar to the rest of [the adverse events]. It's interesting that it looks like TIL can work in the brain.

It's a proof of concept. We know from some studies that ipilimumab/nivolumab or checkpoint inhibitor therapy works just as well as the brain as it does outside the brain, if you're not on steroids.² So theoretically, something like TIL therapy, which you're working on, you're using the exact same T cells. It's just that you're getting them there in a different way. But theoretically, it would work in the brain. It's just that we haven't proven it yet, so I think it does give us a good indication.

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_{DISCLOSURES: Olson previously reported consulting fees from Iovance, Obsidian, Novartis, Aadi.}

REFERENCES

1. Betof Warner A, Smithy JW, Postow MA, et al. A pilot trial of autologous tumor infiltrating lymphocytes (lifileucel, LN-144) for patients with asymptomatic melanoma brain metastases. J Clin Onocl. The 21^st International Congress of the Society For Melanoma Research; October 10-13, 2024; New Orleans, LA.

2. Long GV, Atkinson V, Lo SN, et al. Ipilimumab plus nivolumab versus nivolumab alone in patients with melanoma brain metastases (ABC): 7-year follow-up of a multicentre, open-label, randomised, phase 2 study. Lancet Oncol. 2025;26(3):320-330. doi:10.1016/S1470-2045(24)00735-6