Tumor-Infiltrating Lymphocyte Therapy or Ipilimumab in Advanced Melanoma

被引：303

作者：

Rohaan, Maartje W. ^{[1
]}

Borch, Troels H. ^{[30
]}

van den Berg, Joost H. ^{[2
]}

Met, Ozcan ^{[30
]}

Kessels, Rob ^{[5
]}

Geukes Foppen, Marnix H. ^{[1
]}

Stoltenborg Granhoj, Joachim ^{[30
]}

Nuijen, Bastiaan ^{[3
]}

Nijenhuis, Cynthia ^{[2
]}

Jedema, Inge ^{[4
]}

van Zon, Maaike ^{[2
]}

Scheij, Saskia ^{[2
]}

Beijnen, Jos H.

Hansen, Marten ^{[9
]}

Voermans, Carlijn ^{[9
]}

Noringriis, Inge M. ^{[30
]}

Monberg, Tine J. ^{[30
]}

Holmstroem, Rikke B. ^{[30
]}

Wever, Lidwina D. V. ^{[5
]}

van Dijk, Marloes ^{[5
]}

Grijpink-Ongering, Lindsay G. ^{[5
]}

Valkenet, Ludy H. M. ^{[5
]}

Torres Acosta, Alejandro ^{[5
]}

Karger, Matthias ^{[1
]}

Borgers, Jessica S. W. ^{[1
]}

ten Ham, Renske M. T. ^{[6
,11
]}

Retel, Valesca P. ^{[6
,15
]}

van Harten, Wim H. ^{[6
]}

Lalezari, Ferry ^{[7
]}

van Tinteren, Harm ^{[5
,13
]}

van der Veldt, Astrid A. M. ^{[17
]}

Hospers, Geke A. P. ^{[18
]}

Stevense-den Boer, Marion A. M. ^{[19
]}

Suijkerbuijk, Karijn P. M. ^{[12
]}

Aarts, Maureen J. B. ^{[20
,27
]}

Piersma, Djura ^{[16
]}

van den Eertwegh, Alfons J. M. ^{[10
]}

de Groot, Jan-Willem B. ^{[21
]}

Vreugdenhil, Gerard ^{[22
]}

Kapiteijn, Ellen ^{[23
]}

Boers-Sonderen, Marye J.

Fiets, W. Edward ^{[28
]}

van den Berkmortel, Franchette W. P. J. ^{[29
]}

Ellebaek, Eva ^{[30
]}

Hoelmich, Lisbet R. ^{[31
]}

van Akkooi, Alexander C. J. ^{[8
,32
,33
]}

van Houdt, Winan J. ^{[8
]}

Wouters, Michel W. J. M. ^{[8
,24
]}

van Thienen, Johannes V. ^{[1
,3
]}

Blank, Christian U. ^{[1
]}

机构：

[1] Vrije Univ Amsterdam, Amsterdam Univ Med Ctr, Div Med Oncol, Amsterdam, Netherlands

[2] Vrije Univ Amsterdam, Amsterdam Univ Med Ctr, Hosp Pharm, BioTherapeut Unit, Amsterdam, Netherlands

[3] Vrije Univ Amsterdam, Amsterdam Univ Med Ctr, Div Pharm & Pharmacol, Amsterdam, Netherlands

[4] Vrije Univ Amsterdam, Amsterdam Univ Med Ctr, Mol Oncol & Immunol, Amsterdam, Netherlands

[5] Vrije Univ Amsterdam, Amsterdam Univ Med Ctr, Biometr, Amsterdam, Netherlands

[6] Vrije Univ Amsterdam, Amsterdam Univ Med Ctr, Psychosocial Res & Epidemiol, Amsterdam, Netherlands

[7] Vrije Univ Amsterdam, Amsterdam Univ Med Ctr, Radiol, Amsterdam, Netherlands

[8] Vrije Univ Amsterdam, Amsterdam Univ Med Ctr, Surg Oncol, Amsterdam, Netherlands

[9] Vrije Univ Amsterdam, Amsterdam Univ Med Ctr, Netherlands Canc Inst, Dept Hematopoiesis,Sanquin Res & Landsteiner Lab, Amsterdam, Netherlands

[10] Vrije Univ Amsterdam, Amsterdam Univ Med Ctr, Dept Med Oncol, Amsterdam, Netherlands

[11] Univ Utrecht, Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Dept Healthcare Innovat & Evaluat, Utrecht, Netherlands

[12] Univ Utrecht, Univ Med Ctr Utrecht, Dept Med Oncol, Utrecht, Netherlands

[13] Univ Utrecht, Univ Med Ctr Utrecht, Trial & Data Ctr, Princess Maxima Ctr Pediat Oncol, Utrecht, Netherlands

[14] Univ Utrecht, Univ Med Ctr Utrecht, Oncode Inst, Utrecht, Netherlands

[15] Univ Twente, Dept Hlth Technol & Serv Res, Enschede, Netherlands

[16] Med Spectrum Twente, Dept Med Oncol, Enschede, Netherlands

[17] Erasmus MC, Dept Med Oncol, Rotterdam, Netherlands

[18] Univ Med Ctr Groningen, Dept Med Oncol, Groningen, Netherlands

[19] Amphia Hosp, Dept Med Oncol, Breda, Netherlands

[20] Maastricht Univ Med Ctr, Dept Med Oncol, Maastricht, Netherlands

[21] Isala, Dept Med Oncol, Zwolle, Netherlands

[22] Maxima Med Ctr, Dept Med Oncol, Eindhoven, Netherlands

[23] Leiden Univ, Dept Med Oncol, Med Ctr, Leiden, Netherlands

[24] Leiden Univ, Dept Biomed Data Sci, Med Ctr, Leiden, Netherlands

[25] Leiden Univ, Dept Hematol, Med Ctr, Leiden, Netherlands

[26] Leiden Univ, Dept Clin Oncol, Med Ctr, Leiden, Netherlands

[27] Radboud Univ Nijmegen, Dept Med Oncol, Med Ctr, Nijmegen, Netherlands

[28] Med Ctr Leeuwarden, Dept Med Oncol, Leeuwarden, Netherlands

[29] Zuyderland Med Ctr, Dept Med Oncol, Sittard Geleen, Netherlands

[30] Copenhagen Univ Hosp, Natl Ctr Canc Immune Therapy, Dept Oncol, Herlev, Denmark

[31] Copenhagen Univ Hosp, Dept Plast Surg, Herlev, Denmark

[32] Univ Sydney, Melanoma Inst Australia, Fac Med & Hlth, Sydney, Australia

[33] Royal Prince Alfred Hosp, Sydney, Australia

[34] Netherlands Canc Inst, Div Med Oncol, Plesmanlaan 121, NL-1066 CX Amsterdam, Netherlands

[35] Copenhagen Univ Hosp, Natl Ctr Canc Immune Therapy, Dept Oncol, Borgmester Ib Juuls Vej 25C,5th fl, DK-2730 Herlev, Denmark

来源：

NEW ENGLAND JOURNAL OF MEDICINE | 2022年 / 387卷 / 23期

关键词：

ADOPTIVE CELL THERAPY; METASTATIC MELANOMA; COMPLETE RESPONSES; IMMUNOTHERAPY; GUIDELINES; NIVOLUMAB; OUTCOMES; CANCER;

D O I：

10.1056/NEJMoa2210233

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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.

引用

页码：2113 / 2125

页数：13

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