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.

AU - Meerveld-Eggink, Aafke

AU - Klobuch, Sebastian

AU - Wilgenhof, Sofie

AU - Schumacher, Ton N.

AU - Donia, Marco

AU - Svane, Inge Marie

AU - Haanen, John B.A.G.

N1 - Publisher Copyright: © 2022 Massachusetts Medical Society.

PY - 2022

Y1 - 2022

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 - Dermatology

KW - Hematology/Oncology

KW - Skin Cancer

KW - Treatments in Oncology

U2 - 10.1056/NEJMoa2210233

DO - 10.1056/NEJMoa2210233

M3 - Journal article

C2 - 36477031

AN - SCOPUS:85143690227

VL - 387

SP - 2113

EP - 2125

JO - New England Journal of Medicine

JF - New England Journal of Medicine

SN - 0028-4793

IS - 23

ER -