Lifileucel Shows Promise for Melanoma, Yet Challenges Remain for Community Implementation

Lifileucel (Amtagvi; Iovance Biotherapeutics, Inc), an autologous tumor-infiltrating lymphocyte (TIL) cell therapy, was a standout therapy from data presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting on cutaneous malignancies, according to André Harvin, PharmD, chief pharmacy officer and vice president at Cone Health, during a panel discussion at the Oncology Pharmacists Connect (OPC) meeting in Austin, Texas. Lifileucel was investigated in the phase 2, open-label IOV-COM-202 trial (NCT03645928), which assessed lifileucel combined with pembrolizumab (Keytruda; Merck) in patients who were immune checkpoint inhibitor–naive with unresectable or metastatic melanoma, noted panelist Heidi Gunderson Finnes, PharmD, BCOP, FHOPA, director of clinical ambulatory pharmacy practice at Mayo Clinic, during the OPC session.^1,2

“Patients were allowed to receive—while the lifileucel TIL cells were being manufactured—a dose of pembrolizumab at either the 200 mg every 3 weeks or 400 mg every 6 weeks dose. Once cells were received back from Iovance to the site, they started lymphodepleting chemotherapy with cyclophosphamide plus fludarabine, and the lifileucel cells were given on day 0,” Finnes said. “To support cell expansion, aldesleukin at 600 units per kilogram every 8 to 12 hours was given for up to 6 doses subsequently. Then after 30 days, once the cells were allowed to expand, patients were allowed to start pembrolizumab maintenance therapy at either 200 or 400 milligrams every 3 or 6 weeks for up to 24 months.”¹

Additionally, Finnes noted that since this is a phase 2 trial, the primary end points were investigator-assessed objective response rate (ORR) and incidence of grade 3 or greater treatment-emergent adverse events.¹ However, Finnes explained that the ORR was strong at 63.6% (14/22), including 22.7% (5/22) complete response and 40.9% (9/22) partial response, with 6 patients (27.3%) demonstrating stable disease (SD).^1,2 Further, the median time to initial response was 2.5 months, with all patients with evaluable responses showing regression of target lesions.²

Harvin noted that lifileucel was recently granted accelerated approved by the FDA on February 16, 2024, for adult patients with unresectable or metastatic melanoma who have been previously treated with a PD-1 blocking antibody, and if the patient was BRAF V600 positive, a BRAF inhibitor with or without a MEK inhibitor.^1,3 Following this approval, Harvin noted that there are some challenges with integrating this therapy into clinical practice at community centers not connected with large academic medical centers.¹

Cancer cells observed under a microscope. Image Credit: © Marko - stock.adobe.com

“I represent a community health system, and as we see some of these more complex medications come to the market, there is a feeling of us getting left behind with what we're able to provide for patients in the community [setting] without the resources and infrastructure of a large academic medical center,” Harvin said.¹

Finnes agreed, noting that there is a similar issue with CAR T-cell therapies, as patients most likely need to be treated at an academic medical center to get access to these therapies. One reason for this is storage challenges, according to Finnes.¹

“We know that 80% of our patients are treated in the community, [yet] the storage of these medications is problematic. Lifileucel comes cryopreserved in liquid nitrogen—[but] how many of you have liquid nitrogen tanks that you can store something like that in,” Finnes said. “I think we need to pressure manufacturers to make things that can be delivered and to allow community sites to be able to receive and get these types of medications. Unfortunately, I think with lifileucel…they have to be hospitalized, and that's also problematic for community centers.”¹

Harvin explained that these challenges can result in community cancer centers losing patients to academic medical centers, which can complicate a patient’s care depending on the distance they need to travel to get to that new site of care.¹

From a payer perspective, Laura R. Bobolts, PharmD, BCOP, senior vice president, clinical strategy and growth, OncoHealth, explained that her organization would love to see lifileucel and CAR T-cell therapies become more readily available in the community setting, which is where a majority of patients reside.¹

“Not every patient lives near a large academic center,” Bobolts said. “In Puerto Rico, we have just 1 hospital that just started getting 1 CAR T-cell product, after how many years? So now you have a TIL therapy like lifileucel—how long is that going to take before patients can gain access in the community? So, it's a challenge. But, from a payer [perspective], the bigger challenge is the price.”¹

Bobolts explained that lifileucel currently has a price tag of $515,000, and this does not include the cost of the inpatient stay that is required with treatment of the interleukin-2 therapy aldesleukin.¹

“On the payer side, where it's FDA approved today is unresectable or metastatic melanoma, and it has roughly a 30% change in [ORR],” Bobolts said. “That means about 7 out of 10 patients received this toxic therapy, and over half a million dollars later, 70% didn't respond. So, where's the value?”¹

Additionally, Bobolts noted that the lack of a comparator for lifileucel in the IOV-COM-202 trial raises questions for payers.¹

“The results do look impressive, but [impressive] compared to what? If you're going to have a price tag that's going to make me fall out of my chair, I want to see it have real value,” Bobolts said.¹

Finnes explained that the $515,000 also doesn’t include the treatment of toxicities associated with the therapy.¹

“I do see this as an avenue for pharmacists to have a real role. I have been an oncology pharmacist for 26 years, and I've given aldesleukin only very early in my career, but we put all of those patients in our intensive care unit for monitoring to monitor urine output, blood pressure, all sorts of different things, and that's how you decide whether to give subsequent doses,” Finnes said. “You would have to have monitored beds in order to do that.”¹

Additionally, Finnes noted that another challenge is that the same service team is providing patients with TIL and CAR T-cell therapy, so they may not be willing to give up spaces for patients receiving CAR T for patients to receive TIL.¹

“[TIL] really doesn't have a great comparator,” Finnes said. “I think the concern for me is, again, in a time, when we're being asked to ensure access [for patients], you would have to be an approved site to give this medication. We're trying to improve access and give equal therapies to disparate populations, [and] this really selects out that type of thing. I think, again, a cost-benefit analysis is definitely going to be needed.”¹

Finnes explained further that since there is no long term follow up data available yet, it is hard to know whether this therapy is going to remain in the treatment armamentarium for melanoma long term. However, Finnes noted that lifileucel may expand into other disease states outside melanoma in the future.¹

On the payer side, Bobolts noted that payers are bound by extensive regulations in regard to coverage of lifileucel. According to Bobolts, coverage will lie where the FDA approved indication is, which remains third-line or later metastatic melanoma.¹

“If it is being used as FDA approved today, more than likely it's covered. It’s mandated to be covered for Medicare and more than likely for Medicaid [as well],” Bobolts said.¹

However, commercial payers can be stricter in terms of coverage, according to Bobolts. Although the new data from ASCO show adding pembrolizumab to lifileucel has benefit, if the regimen is not FDA approved, not published in full text, and not included in National Comprehensive Cancer Network’s compendium, coverage from commercial payers for that doublet therapy in the front line may not be secured.¹

Harvin also noted that he has questions regarding the generalizability of the IOV-COM-202 trial data, as the population included in the study were overwhelmingly White and male. Finnes noted that much of the accrual for the phase 3 trial is occurring in Australia and Europe, with some sites open in North America, so the issue of generalizability of the data may remain a concern depending on the accrued population characteristics.¹

REFERENCES

1. Harvin AD, Finnes HG, Bobolts LR. A Deep Dive Into Modern Treatment Approaches for Cutaneous Malignancies. Oncology Pharmacists Connect; June 20-21; Austin, Texas.
2. Thomas SS, Gogas H, Hong YK, et al. Efficacy and safety of lifileucel, an autologous tumor-infiltrating lymphocyte cell therapy, and pembrolizumab in patients with immune checkpoint inhibitor-naive unresectable or metastatic melanoma: Updated results from IOV-COM-202 cohort 1A. J Clin Onc. 2024;42(suppl 16). doi:10.1200/JCO.2024.42.16_suppl.9505
3. FDA grants accelerated approval to lifileucel for unresectable or metastatic melanoma. FDA. February 16, 2024. Accessed June 20, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-lifileucel-unresectable-or-metastatic-melanoma