Tumor-infiltrating lymphocyte therapy or ipilimumab in advanced melanoma

Rohaan, M.W.; Borch, T.H.; Berg, J.H. van den; Met, O.; Kessels, R.; Foppen, M.G.H.; ... ; Haanen, J.B.A.G. (2022)

Article / Letter to editor

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 5x10(9) 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.

• All authors: Rohaan, M.W.; Borch, T.H.; Berg, J.H. van den; Met, O.; Kessels, R.; Foppen, M.G.H.; Granhoj, J.S.; Nuijen, B.; Nijenhuis, C.; Jedema, I.; Zon, M. van; Scheij, S.; Beijnen, J.H.; Hansen, M.; Voermans, C.; Noringriis, I.M.; Monberg, T.J.; Holmstroem, R.B.; Wever, L.D.V.; Dijk, M. van; Grijpink-Ongering, L.G.; Valkenet, L.H.M.; Acosta, A.T.; Karger, M.; Borgers, J.S.W.; Ham, R.M.T. ten; RetFl, V.P.; Harten, W.H. van; Lalezari, F.; Tinteren, H. van; Veldt, A.A.M. van der; Hospers, G.A.P.; Stevense-den Boer, M.A.M.; Suijkerbuijk, K.P.M.; Aarts, M.J.B.; Piersma, D.; Eertwegh, A.J.M. van den; Groot, J.W.B. de; Vreugdenhil, G.; Kapiteijn, E.; Boers-Sonderen, M.J.; Fiets, W.E.; Berkmortel, F.W.P.J. van den; Ellebaek, E.; Holmich, L.R.; Akkooi, A.C.J. van; Houdt, W.J. van; Wouters, M.W.J.M.; Thienen, J.V. van; Blank, C.U.; Meerveld-Eggink, A.; Klobuch, S.; Wilgenhof, S.; Schumacher, T.N.; Donia, M.; Svane, I.M.; Haanen, J.B.A.G.
• Date: 2022-12-08
• Journal: New England Journal of Medicine
• Volume: 387
• Issue: 23
• Pages: 2113 - 2125
• DOI: doi:10.1056/NEJMoa2210233