Awareness of TIL Therapy for Melanoma Is Crucial for Timely Referral

Adoptive cell therapy with tumor-infiltrating lymphocytes (TILs) is a promising development in metastatic melanoma, a setting where immunotherapies have already dramatically improved outcomes for patients. The FDA-approved autologous TIL therapy approach requires coordination with an authorized treatment center, explained Barbara T. Ma, MD, MS, assistant professor of medicine at Weill Cornell Medicine and assistant attending physician at New York Presbyterian Hospital, in a recent in-person Community Case Forum meeting in New York City. Ma discussed the process of determining patient eligibility for TILs and outlined the process of treatment, which requires an inpatient hospital stay and comes with initial toxicities primarily seen during inpatient administration.

Targeted Oncology: What determines a patient’s eligibility for TIL to treat metastatic melanoma?

Barbara T. Ma, MD, MS: TILs are a cell therapy process. [Lifileucil (Amtagvi)] is FDA approved for patients with metastatic or unresectable melanoma who had progression on prior immunotherapy, and if they have a BRAF mutation, [they must have] had progression on prior targeted therapy.¹ They have to have sufficient cardiac and pulmonary reserve, no active brain metastases, and no active immune-related adverse events [AEs] requiring steroids, because steroids tend to limit TIL yield. In terms of what they're making the TIL from, it's procured from a chunk of tumor, so there has to be a resectable lesion that's a minimum of 1.5 cm. They have to be a relatively fit patient. In terms of contraindications, they must not have active brain metastases, have good kidney function, have controlled infections, and not be on any chronic steroids at greater than 10 mg of prednisone or equivalent.

What is the process of receiving TIL therapy?

TILs are from the patient's own tumor, so they see a surgeon [and] the surgeon takes a chunk of the tumor, and it has to be a minimum of 1.5 cm. They send it to an outside company, where they isolate out these TILs. It takes anywhere from 3 to 5 weeks for the cell product to be ready, and after that, the patient undergoes a lymphodepleting chemotherapy, usually fludarabine and cyclophosphamide. This can happen in the inpatient or outpatient setting, but essentially this is to make it so that it is a better environment for the TILs to work.

The TILs get infused, and this part is inpatient, plus the IL-2 [interleukin-2] administration. IL-2 is given for a maximum of 6 doses every 8 to 12 hours. But essentially, the purpose of the IL-2 is to expand the TILs in vivo, and the bulk of the toxicity usually comes right after this lymphodepleting regimen, because it's a hefty chemotherapy that you'll see when you're doing conditioning for chimeric antigen receptor T-cell therapy, [etc]. The patients get cytopenic, and it happens at the same time that they're getting the TIL infusion and the IL-2. Since IL-2 can cause fever, renal toxicity, and a slew of inflammatory AEs, this is why this has to be in the inpatient setting. But it also needs a center that's experienced with IL-2. The bulk of the toxicity is in this [time period], and patients get discharged when they have [blood cell] count recovery and are fever free. On average, this is probably a 2 and a half to 3 weeks of hospitalization, if you're also doing the lymphodepletion inpatient. Most centers are playing around with inpatient vs outpatient, but I think the majority are doing inpatient right now.

What is important to know about using high-dose IL-2 and monitoring patients?

The concept of high-dose IL-2 has been around for a while, and they used to give up to 15 doses of IL-2. But for lifileucel, they give up to 6 doses every 8 to 12 hours, and you get a lot of AEs. But the point is that you need a lot of monitoring, so that's why it needs an inpatient hospitalization, but also a team that's experienced with knowing how to manage the toxicity.

The parameters for discharge are [absolute neutrophil] count recovery and [being] afebrile for 24 hours after stopping intravenous antibiotics. Patients are on prophylactic antivirals and antibiotics. Usually for 30 days post the TIL infusion, they're encouraged to remain close to the treatment center. If they require transfusions because they're still cytopenic; that's part of the reason for the close monitoring, but the bulk of the toxicity is in the initial 14 days.

There are only a certain number of authorized treatment centers throughout the country, but there are places that I know are getting set up to do that. But the point is that you require coordination with an experienced team, so it's a complex process. Why do we do this? Because it's a shot at a durable response. I know it can sound like a barrier, meaning that it can sound intimidating to a patient, but in general, you need a team that's experienced.

What is the role of the community oncologist for TIL therapy?

There has to be increased awareness, both on the patient side and physician side. On the community side, it does require coordination with the multidisciplinary team and a timely referral since the treatment window can be narrow, especially in patients whose disease is rapidly progressing. Also, the initial toxicities are in the first 30 days, but the follow-up can be either with the primary [physician] or the cell therapy specialist.

DISCLOSURES: There are no known relevant disclosures.

_REFERENCE:

_{Betof Warner A, Hamid O, Komanduri K, et al. Expert consensus guidelines on management and best practices for tumor-infiltrating lymphocyte cell therapy. J Immunother Cancer. 2024;12(2):e008735. doi:10.1136/jitc-2023-008735}