Tumor-Infiltrating Lymphocyte Therapy for Melanoma

MedMaven

by Dr. C.H. Weaver M.D. 1/2020

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 2019 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%).

With a median follow-up was 7.4 months 38% of patients responded to treatment including two complete responses, 23 partial responses and 28 patients with stable disease. The overall disease control rate was 80%. 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.

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