Adoptive transfer of tumor-infiltrating lymphocytes in patients with metastatic melanoma: intent-to-treat analysis and efficacy after failure to prior immunotherapies

The Ella Lemelbaum Institute at Sheba Medical Center began treating metastatic melanoma with autologous tumour-infiltrating lymphocytes in 2006, more than a decade before any regulator approved the approach. This report is the intent-to-treat analysis of the first 80 patients with stage IV disease enrolled in the programme.

Tumour-infiltrating lymphocyte cultures could be established for 72 of the 80. Fifty-seven were treated with unselected or young lymphocytes and high-dose interleukin-2 after non-myeloablative lymphodepleting conditioning. Twenty-three were withdrawn, mostly because they deteriorated clinically during the weeks the cells were being grown, which is the cost of a manufacturing step that cannot be hurried.

The overall response rate was 29 percent and median survival 9.8 months counting everyone enrolled; 40 percent and 15.2 months counting those actually treated. Five patients achieved complete and 18 partial remission. Every complete responder remained in unmaintained remission at a median follow-up of 28 months, and three-year survival among responders was 78 percent. On multivariate analysis, lactate dehydrogenase, sex, days of culture and the total number of infused CD8-positive cells independently predicted outcome. Thirty-two patients received ipilimumab before or after the cells; patients who had not responded to ipilimumab or interleukin-2 did about as well on cell therapy as those who had.