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Criteria and Considerations for Using Newly FDA-Approved Lifileucel in Advanced Melanoma

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March 6, 2024

Clinical relevance: Lifileucel’s FDA approval offers physicians a groundbreaking treatment option for advanced melanoma, potentially transforming patient care. Experts expect similar treatments for solid tumors to follow.


Oncologists should consider incorporating tumor-infiltrating lymphocyte (TIL) therapy into their treatment plans for advanced melanoma, following the FDA’s historic accelerated approval of lifileucel (Amtagvi). This marks a groundbreaking milestone in the use of TILs in oncology.

According to Dr. Rodabe Amaria, an associate professor of melanoma at The University of Texas MD Anderson Cancer Center, the move signifies a transformative leap forward in cellular therapy. 

“FDA approval of lifileucel is monumental since it represents over 30 years of research focusing on harnessing the power of T cells for oncology treatment,” Dr. Amaria tells SurivorNet.

The approval is a first for a cellular therapy targeting a solid tumor. It underscores the ongoing evolution in cancer treatment and highlights the critical role of innovative therapies have in extending quality of life and survival for patients with advanced-stage diseases.

This development also provides a new avenue for physicians to explore, especially when considering treatment options for patients nearing the end of life.

It reinforces the importance of personalized medicine in oncology that assesses each patient’s unique situation to decide upon the viability and potential benefits of late-stage immunotherapy.

Related: Melanoma Clinical Trial

What is TIL Therapy?

Unlike CAR T-cell therapies, which modify T cells from circulating blood, lifileucel harnesses T cells directly from the patient’s tumor.

TILs are inherently primed to combat cancer. In the case of lifileucel therapy, they amplify their antitumor efficacy significantly. 

Treatment entails extracting TILs directly from the tumor mass, expanding their numbers ex vivo, and then reinfusing the enhanced cells back into the patient. This augmented TIL army intensifies the immune response against cancer, leading to tumor reduction or eradication in some cases. 

“The process of treating a patient with TIL is highly complicated with a number of distinct components. An essential detail is in perfecting the methodology to grow good quality T cells in a short period of time in a way that maintains the highest standard of patient safety and lifileucel is the first cellular therapy in solid tumors to meet and exceed these standards,” Dr. Amaria says.

It’s worth noting that, while metastatic melanoma constitutes only about 1% of skin cancer cases, it is responsible for a disproportionate share of cancer fatalities. 

The FDA’s approval of lifileucel also signals the potential applicability of TIL-based therapies across a broad spectrum of cancers, potentially impacting up to 90% of all cancer types.

“Melanoma is the gateway tumor and once a new immunotherapy has proven efficacy in melanoma, there is great interest in expanding reach into other solid tumors and thus expanding the reach of this type of treatment,” Dr. Amaria says.

Watch: Dr. Cecelia Larocca on Immunotherapy for Melanoma

Ideal Candidates

Patients most likely to benefit from lifileucel include:

  • Patients with metastatic melanoma
  • Patients who have undergone previous treatment without success
  • Patients previously treated with specific therapies targeting the PD-1 protein
  • Patients unsuccessfully treated for the BRAF mutation specifically at V600.

The Evidence

Although lifileucel was granted accelerated approval by the FDA, the agency has signaled that it wants more information to fully confirm its benefits and safety before granting full approval.

The current approval was bestowed based on the results of a phase 2 clinical trial involving 73 patients treated with the investigational drug:

  • The overall response rate (ORR) was 31.5%, indicating the proportion of patients who achieved partial or complete response to the therapy.
  • Complete response (CR), defined as the total disappearance of all target lesions, was observed in 3 patients.
  • Partial response (PR), reflecting a significant reduction in tumor burden, was achieved by 20 patients, contributing to the overall beneficial response rate.
  • Progression-free survival (PFS) rates at six, nine, and twelve months demonstrated a significant percentage of patients experienced no disease progression or mortality. These findings indicate the therapy’s potential in delaying disease progression and extending survival in treated patients.

Lifileucel was found safe. However, the full treatment regimen did carry side effects, such as nausea, fatigue and risk of other illnesses, which were generally considered manageable and a reasonable tradeoff given the drug’s potential benefit for treating an otherwise deadly cancer.

Side effects specific to the drug included rapid heart rate, fluid build up, rash, hair loss and respiratory difficulties.

Looking Forward

A larger Phase 3 trial is currently underway to confirm lifileucel’s success in treating metastatic melanoma. If the trial has good results, it should lead to the drug’s full FDA approval.

As Dr. Amaria notes, TIL therapy is being looked at for treating other cancers as well. 

“The current Phase 3 doesn’t include any major tweaking of manufacturing to improve outcomes. However, there are a number of ongoing clinical trials looking to genetically manipulate TIL to hopefully make them more effective and to improve on safety,” he says.

Of concern, one recent TIL trial looking at non-small cell lung cancer was stopped after a participant died. The trialists surmised that the death could have been related to chemotherapy or interleukin 2 versus the TIL.