Randomized, Prospective Evaluation Comparing Intensity of Lymphodepletion Before Adoptive Transfer of Tumor-Infiltrating Lymphocytes for Patients With Metastatic Melanoma

Abstract

Adoptive cell transfer, the infusion of large numbers of activated autologous lymphocytes, can mediate objective tumor regression in a majority of patients with metastatic melanoma (52 of 93; 56%). Addition and intensification of total body irradiation (TBI) to the preparative lymphodepleting chemotherapy regimen in sequential trials improved objective partial and complete response (CR) rates. Here, we evaluated the importance of adding TBI to the adoptive transfer of tumorinfiltrating lymphocytes (TIL) in a randomized fashion. Patients and MethodsA total of 101 patients with metastatic melanoma, including 76 patients with M1c disease, were randomly assigned to receive nonmyeloablative chemotherapy with or without 1,200 cGy TBI before transfer of tumor-infiltrating lymphcytes. Primary end points were CR rate (as defined by Response Evaluation Criteria in Solid Tumors v1.0) and overall survival (OS). Clinical and laboratory data were analyzed for correlates of response.Results CR rates were 24% in both groups (12 of 50 v 12 of 51), and OS was also similar (median OS, 38.2 v 36.6 months; hazard ratio, 1.11; 95% CI, 0.65 to 1.91; P = .71). Thrombotic microangiopathy was an adverse event unique to the TBI arm and occurred in 13 of 48 treated patients. With a median potential follow-up of 40.9 months, only one of 24 patients who achieved a CR recurred. ConclusionAdoptive cell transfer can mediate durable complete regressions in 24% of patients with metastatic melanoma, with median survival . 3 years. Results were similar using chemotherapy preparative regimens with or without addition of TBI.

Inhibition of AKT signaling uncouples T cell differentiation from expansion for receptor-engineered adoptive immunotherapy

“…several clinical trials testing tumor infiltrating lymphocytes (TIL) (8)(9)(10) and receptor-engineered T cells (11). Similarly, infusion of less-differentiated T cell subsets that coexpress lymphoid homing markers like CD62L or costimulatory markers such as CD27 are associated with greater tumor regression (12)(13)(14).…”

Immunooncology in Breast Cancer: Active and Passive Vaccination Strategies

“…A classic example of this type of therapy is the adoptive T-cell transfer in malignant melanoma, in which peritumoral T cells are extracted and activated and propagated outside the body. After transfer of these activated T cells, a long-lasting response could be detected in over 25% of the tumors [31].…”

When to Consider Alternatives to Front-Line Immune Therapies in Metastatic Melanoma

“…Retrospective studies have demonstrated a response rate of 16% with approximately 6% with prolonged survival over 10 years [2]. By collection, expansion and reintroduction of a patient's existing tumor infiltration lymphocytes, adoptive cell transfer therapy has demonstrated a response rate as high as 53% in a 'highly select population' [22].…”