Tumor-Infiltrating Lymphocyte Therapy or Ipilimumab in Advanced Melanoma.
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Background Immune checkpoint inhibitors and targeted therapies have dramatically improved outcomes in patients with advanced melanoma, but approximately half these patients will not have a durable benefit. Phase 1-2 trials of adoptive cell therapy with tumor-infiltrating lymphocytes (TILs) have shown promising responses, but data from phase 3 trials are lacking to determine the role of TILs in treating advanced melanoma. Methods In this phase 3, multicenter, open-label trial, we randomly assigned patients with unresectable stage IIIC or IV melanoma in a 1:1 ratio to receive TIL or anti-cytotoxic T-lymphocyte antigen 4 therapy (ipilimumab at 3 mg per kilogram of body weight). Infusion of at least 5×109 TILs was preceded by nonmyeloablative, lymphodepleting chemotherapy (cyclophosphamide plus fludarabine) and followed by high-dose interleukin-2. The primary end point was progression-free survival. Results A total of 168 patients (86% with disease refractory to anti-programmed death 1 treatment) were assigned to receive TILs (84 patients) or ipilimumab (84 patients). In the intention-to-treat population, median progression-free survival was 7.2 months (95% confidence interval [CI], 4.2 to 13.1) in the TIL group and 3.1 months (95% CI, 3.0 to 4.3) in the ipilimumab group (hazard ratio for progression or death, 0.50; 95% CI, 0.35 to 0.72; P<0.001); 49% (95% CI, 38 to 60) and 21% (95% CI, 13 to 32) of the patients, respectively, had an objective response. Median overall survival was 25.8 months (95% CI, 18.2 to not reached) in the TIL group and 18.9 months (95% CI, 13.8 to 32.6) in the ipilimumab group. Treatment-related adverse events of grade 3 or higher occurred in all patients who received TILs and in 57% of those who received ipilimumab; in the TIL group, these events were mainly chemotherapy-related myelosuppression. Conclusions In patients with advanced melanoma, progression-free survival was significantly longer among those who received TIL therapy than among those who received ipilimumab.
Originalsprog | Engelsk |
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Tidsskrift | New England Journal of Medicine |
Vol/bind | 387 |
Udgave nummer | 23 |
Sider (fra-til) | 2113-2125 |
Antal sider | 13 |
ISSN | 0028-4793 |
DOI | |
Status | Udgivet - 2022 |
Bibliografisk note
Funding Information:
Supported by the Dutch Cancer Society , the Netherlands Organization for Health Research and Development , the Dutch Ministry of Health , Stichting Avento , the Antoni van Leeuwenhoek Foundation , Copenhagen University Hospital (Herlev), the Danish Cancer Society , and the Capital Region of Denmark Research Foundation .
Publisher Copyright:
© 2022 Massachusetts Medical Society.
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