TY - JOUR
T1 - Tumor-Infiltrating Lymphocyte Therapy or Ipilimumab in Advanced Melanoma
AU - Rohaan, Maartje W
AU - Borch, Troels H
AU - van den Berg, Joost H
AU - Met, Özcan
AU - Kessels, Rob
AU - Geukes Foppen, Marnix H
AU - Stoltenborg Granhøj, Joachim
AU - Nuijen, Bastiaan
AU - Nijenhuis, Cynthia
AU - Jedema, Inge
AU - van Zon, Maaike
AU - Scheij, Saskia
AU - Beijnen, Jos H
AU - Hansen, Marten
AU - Voermans, Carlijn
AU - Noringriis, Inge M
AU - Monberg, Tine J
AU - Holmstroem, Rikke B
AU - Wever, Lidwina D V
AU - van Dijk, Marloes
AU - Grijpink-Ongering, Lindsay G
AU - Valkenet, Ludy H M
AU - Torres Acosta, Alejandro
AU - Karger, Matthias
AU - Borgers, Jessica S W
AU - Ten Ham, Renske M T
AU - Retèl, Valesca P
AU - van Harten, Wim H
AU - Lalezari, Ferry
AU - van Tinteren, Harm
AU - van der Veldt, Astrid A M
AU - Hospers, Geke A P
AU - Stevense-den Boer, Marion A M
AU - Suijkerbuijk, Karijn P M
AU - Aarts, Maureen J B
AU - Piersma, Djura
AU - van den Eertwegh, Alfons J M
AU - de Groot, Jan-Willem B
AU - Vreugdenhil, Gerard
AU - Kapiteijn, Ellen
AU - Boers-Sonderen, Marye J
AU - Fiets, W Edward
AU - van den Berkmortel, Franchette W P J
AU - Ellebaek, Eva
AU - Hölmich, Lisbet R
AU - van Akkooi, Alexander C J
AU - van Houdt, Winan J
AU - Wouters, Michel W J M
AU - van Thienen, Johannes V
AU - Blank, Christian U
N1 - 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.
PY - 2022/12/8
Y1 - 2022/12/8
N2 - 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.
AB - 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.
KW - Cell- and Tissue-Based Therapy
KW - Humans
KW - Immunotherapy, Adoptive
KW - Ipilimumab/adverse effects
KW - Lymphocytes, Tumor-Infiltrating
KW - Melanoma/drug therapy
KW - Metastatic melanoma
KW - Adoptive cell therapy
KW - Complete responses
KW - Outcomes
KW - Guidelines
KW - Immunotherapy
KW - Nivolumab
KW - Cancer
U2 - 10.1056/NEJMoa2210233
DO - 10.1056/NEJMoa2210233
M3 - Article
C2 - 36477031
SN - 0028-4793
VL - 387
SP - 2113
EP - 2125
JO - New England Journal of Medicine
JF - New England Journal of Medicine
IS - 23
ER -