1048O - Adoptive cell therapy with tumor infiltrating lymphocytes and intermediate dose interleukin-2 for metastatic melanoma

Date 27 September 2014
Event ESMO 2014
Session Immunotherapy of cancer
Topics Cancer Immunology and Immunotherapy
Melanoma and other Skin Tumours
Translational Research
Presenter Rikke Andersen
Citation Annals of Oncology (2014) 25 (suppl_4): iv361-iv372. 10.1093/annonc/mdu342
Authors R. Andersen1, M. Donia1, E. Ellebaek Steensgaard1, T. Holz Borch1, T. Zeeberg Iversen1, P. Kongsted1, M. Hald Andersen2, P. Thor Straten2, I.M. Svane1
  • 1Center For Cancer Immune Therapy, Dept. Of Haematology And Dept. Of Oncology, Herlev Hospital, 2730 - Herlev/DK
  • 2Center For Cancer Immune Therapy, Dept. Of Haematology, Herlev Hospital, 2730 - Herlev/DK

 

Abstract

Aim

Adoptive cell therapy (ACT) with tumor infiltrating lymphocytes (TILs) achieved impressive clinical results in several single institution phase I/II clinical trials performed outside Europe, and holds the promise to enter the mainstream of standard melanoma care in the near future. However, although transient, the toxicities associated with high-dose interleukin-2 (IL-2) classically administered together with TILs are severe and recent results have questioned its use. To further scrutinize IL-2 dosing, we have carried out a phase II trial using TILs after classical lymphodepletion but followed by an attenuated regimen of IL-2.

Methods

A total of 25 patients with progressive metastatic melanoma, PS ≤1, age <70 and at least one resectable metastasis was included in this phase II study (NCT00937625). TIL infusion was preceded by standard lymphodepleting chemotherapy but followed by an intravenous intermediate dose IL-2 decrescendo regimen.

Results

The trial is fully recruited. Data indicate that the lower dose of IL-2 considerably decreased the toxicity of the treatment, and imaging evaluations of the first 20 patients evaluated showed two complete responses (29 + , 15+ months) and seven partial responses (28 + , 12, 19 + , 12 and 11 + , 8, 5+ months) with most responses still ongoing. Clinical responses were associated with high numbers of tumor reactive T-cells infused. Importantly, in most responding patients we observed induction and durable persistence of anti-melanoma T-cell responses in the peripheral blood. Updated results will be presented at the 2014 ESMO conference.

Conclusions

As the first European institution we show that TIL-based ACT is reliable, logistically feasible to administer and clinically effective in metastatic melanoma. Importantly, a high response rate including long-lasting complete responses can be induced after treatment with TILs followed by an attenuated regimen of IL-2, which considerably reduced the occurrence of severe side effects. Effective TIL treatment is associated with induction and long-term persistence in the blood of T cells producing in vitro anticancer responses.

Disclosure

All authors have declared no conflicts of interest.