Streamlining TIL Cell Therapy: ACCC Resources to Improve Referral Pathways and Academic–Community Coordination

Since the 1980s, tumor-infiltrating lymphocyte (TIL) cell therapy has been under investigation as a promising cancer treatment option, but many challenges stood in the way of advancing the treatment from bench to bedside, until now. Last year, lifileucel—the first TIL therapy—was approved for patients with unresectable or metastatic melanoma previously treated with a PD-1 blocking agent and a BRAF inhibitor (with or without a MEK inhibitor), if BRAF V600E mutation positive.

A Milestone in Cancer Treatment 

The premise of TIL cell therapy is to use a patient’s own tumor-infiltrating lymphocytes from the tumor microenvironment to target the cancer. In this process, TILs are harvested from the patient’s tumor sample and amplified in a laboratory, after which they are infused back into the patient for a more robust response. Unlike chimeric antigen receptor (CAR) T-cell therapy, where a patient’s own T cells are engineered to target specific cancer antigens, TIL cell therapy leverages the innate heterogeneity of tumor-infiltrating lymphocytes that already recognize an array of cancer antigens.

In its initial phase 2 study, lifileucel demonstrated an impressive response rate of 31.4%, with nearly 42% of responses lasting for at least 18 months. Data from a subsequent 5-year analysis from the same clinical trial showed a median duration of response of 36.5 months and an overall survival rate of 19.7% at the 5-year assessment time point.

As a one-time treatment with long-lasting results, TIL cell therapy fills an important need for patients with metastatic melanoma who have progressed on initial therapies. However, similar to CAR T-cell therapy, TIL cell therapy is fraught with complexities and logistics that can be difficult to navigate. To support earlier identification of potential candidates and strengthen coordination between referring programs and treatment centers, ACCC is excited to share its new provider resources for TIL cell therapy, including a referral readiness checklist, patient pathway guide, and white paper with tangible steps for improving access. 

Challenges in Transitioning Care 

TIL cell therapy and its ancillary processes are administered at authorized treatment centers (ATCs); close collaboration between non-ATC referring programs and ATCs is paramount to ensuring that patients have access to TIL cell therapy when appropriate. 

Sara Cobb, clinical nurse manager of the cellular immunotherapy program at Massachusetts General Hospital (an ATC for TIL cell therapy) and member of ACCC’s TIL cell therapy program advisory committee, notes that “transitioning from [the] community provider to an academic center is a significant challenge for many patients. ACCC resources, which clarify the referral process and patient treatment journey, are invaluable in guiding the initial conversations patients have with their treatment team, nurses, APPs, and physicians. ACCC’s TIL cell therapy toolkit offers practical, evidence-based guidance that helps us streamline our workflows, educate our teams, and ensure patients receive timely, coordinated access to advanced treatments.” 

Eligibility Criteria 

As part of TIL cell therapy, patients undergo non-myeloablative lymphodepleting chemotherapy to prepare the tumor microenvironment to receive TIL cells. After TIL infusion, patients receive a short course of high-dose IL-2 to boost the effects of TIL. Thus, to be a candidate for TIL, patients must have sufficient performance status to tolerate lymphodepleting chemotherapy and subsequent IL-2 treatment.

Compared with supplementary treatments, TIL cell therapy itself is associated with minimal adverse events and is not affiliated with cytokine release syndrome (CRS) or immune effector cell-mediated neurotoxicity syndrome (ICANS) in the same way that CAR T-cell therapy is. Furthermore, patients must have a surgically accessible tumor lesion that can provide a specimen of at least 1.5 cm for TIL production. Laboratory processing of TILs can take 4–6 weeks; thus, patients must have disease that is stable enough to wait this period of time.

Bringing Care Coordination to the Forefront 

Due to the time-sensitive nature of the TIL cell therapy process, early patient education and timely referral help avoid treatment delays. However, community oncologists have reported a lack of patient-friendly resources to discuss TIL cell therapy. In addition, referring clinicians need better guidance on which patients to refer and when to refer them. To help providers identify which patients would be appropriate for TIL, ACCC has developed the Referral Pathway and Readiness Checklist. This resource discusses the process of assessing patient eligibility, alleviating caregiver burden, and overcoming logistical barriers to facilitate access to TIL cell therapy.

Once a patient is deemed eligible and a decision is made to pursue TIL cell therapy, the patient’s care will be transferred to the ATC. During this time, referring practices have found that it is more efficient to have a single point of contact at the ATC, such as a navigator or coordinator. After completing TIL cell therapy, patients will remain under the care of the ATC for acute follow-up before they return to their community oncologist for ongoing follow-up care.

Best Practices for Post-Treatment Care 

In the long-term setting, referring providers have reported that it can be unclear what their responsibilities should be once receiving the patient back in their care. A best practice identified by ACCC focus groups is for ATCs to create structured discharge summaries complete with monitoring timelines, follow-up plans, and contact information.

In response to the various challenges encountered throughout the TIL cell therapy process, ACCC recommends several important action items for referring practices to implement: 

• Establishing processes for early eligibility identification, patient education, and proactive referrals 
• Setting realistic expectations with patients about the treatment process, recovery, and the role of caregivers 
• Screening for needs related to social determinants of health 
• Proactively addressing potential barriers (eg, transportation or accommodation needs) 
• Establishing and maintaining direct communication with the ATC coordinator 
• Requesting comprehensive post-TIL treatment summaries and guidance for managing both current and potential long-term toxicities 
• Scheduling post-TIL cell therapy follow-up visits.

Empowering Providers and Patients 

TIL cell therapy is a critical milestone in the journey of melanoma treatment, and “making physicians and eligible patients aware of this treatment option is exciting and at the core of the ACCC’s TIL advisory committee mission,” according to Dr. Sigrun Hallmeyer, medical director of Advocate Lutheran General Hospital’s Cancer Service Line and member of ACCC’s TIL advisory board. ACCC’s TIL cell therapy resources empower referring providers with the necessary tools to identify eligible patients promptly and streamline care coordination with ATCs.