Tumor-Infiltrating Lymphocyte Therapy for Melanoma

MedMaven

by Dr. C.H. Weaver M.D. 6/2020

Adoptive cell transfer with autologous tumor-infiltrating lymphocytes (TILS) show promising overall response rates for the treatment of recurrent/refractory melanoma according to clinical trial results presented at the 2020 ASCO Annual Meeting. Initial data show that investigational therapy with TILD had a 38% overall response rate among patients with advanced melanoma.

TILS are a type of adoptive cellular therapy (ACT) in which T cells are isolated based on their tumor-specific antigen recognition and then expanded outside the body and infused back into the patient.

Tumor infiltrating lymphocytes and ones that have penetrated the stroma of a tumor and are largely comprised of T cells that are actively engaged in fighting the cancer. TIL therapy requires that a tumor biopsy be taken from the patient from which DNA isolated from the tumor can be sequenced to identify mutations found in the cancer. TILs that can recognize the cancer are then selected, expanded, and transfused back into the patient.

In the current trial a patient’s TILs from a resected portion of their tumor were isolated and then expanded in a laboratory. The manufacturing process takes 22 days. Patients then underwent lymphodepletion for 1 week with cyclophosphamide or fludarabine and were given up to six doses of interleukin-2 after the infusion of the Lifileucel TILS. The entire process takes about 2 weeks from the start of lymphodepletion, followed by TIL infusion, ending with adjuvant interleukin-2 therapy.

Sixty-six patients with stage IIIC or stage IV metastatic melanoma were infused with cryopreserved Lifileucel TILs. Patients had previously received an average of 3 previous therapies before infusion, including PD-1 inhibitors (100%), CTLA-4 inhibitors (80%) and BRAF/MEK inhibitors (23%).

Median follow-up was 18.7 months 36% of patients have responded to treatment including two complete responses and 22 partial responses. Twenty-nine patients (44%) had stable disease, for a disease control rate of 80%. Thus far responses appear to be durable. The median duration of response is not yet reached, with a range of 2.2 months to beyond 26.9 months.

The most common side effects included thrombocytopenia, chills, anemia, and febrile neutropenia. Overall 95% of patients experienced side effects and two patients died from complications of treatment.

Melanoma is known to be responsive to immunotherapy in general in these data suggest that treatment with TILS is very encouraging and could represent an advance in the overall management for individuals with advanced melanoma.

References:

  1. Sarnaik A, et al. Abstract 2518. Presented at: ASCO Annual Meeting; May 31-June 4, 2019; Chicago.
  2. Jazaeri AA, et al. Abstract 2538. Presented at: ASCO Annual Meeting; May 31-June 4, 2019; Chicago.
  3. Long-term follow up of lifileucel (LN-144) cryopreserved autologous tumor infiltrating lymphocyte therapy in patients with advanced melanoma progressed on multiple prior therapies.
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