Late immune-related adverse events in long-term responders to PD-1/PD-L1 checkpoint inhibitors: A multicentre study

被引：53

作者：

Nigro, Olga ^{[1
]}

Pinotti, Graziella ^{[1
]}

De Galitiis, Federica ^{[2
]}

Di Pietro, Francesca Romana ^{[2
,3
]}

Giusti, Raffaele ^{[3
]}

Filetti, Marco ^{[3
]}

Bersanelli, Melissa ^{[4
]}

Lazzarin, Alessandro ^{[4
]}

Bordi, Paola ^{[4
]}

Catino, Annamaria ^{[5
]}

Pizzutilo, Pamela ^{[5
]}

Galetta, Domenico ^{[5
]}

Marchetti, Paolo ^{[2
,6
]}

Botticelli, Andrea ^{[6
]}

Scagnoli, Simone ^{[6
]}

Russano, Marco ^{[7
]}

Santini, Daniele ^{[7
]}

Torniai, Mariangela ^{[8
]}

Berardi, Rossana ^{[8
]}

Ricciuti, Biagio ^{[9
]}

De Giglio, Andrea ^{[9
]}

Chiari, Rita ^{[10
]}

Russo, Alessandro ^{[11
]}

Adamo, Vincenzo ^{[11
]}

Tudini, Marianna ^{[12
]}

Silva, Rosa Rita ^{[12
]}

Bolzacchini, Elena ^{[13
]}

Giordano, Monica ^{[13
]}

Di Marino, Pietro ^{[14
]}

De Tursi, Michele ^{[15
]}

Rijavec, Erika ^{[16
]}

Ghidini, Michele ^{[16
]}

Vallini, Ilaria ^{[1
]}

Stucci, Luigia Stefania ^{[17
]}

Tucci, Marco ^{[17
,25
]}

Pala, Laura ^{[18
]}

Conforti, Fabio ^{[18
]}

Queirolo, Paola ^{[18
]}

Tanda, Enrica ^{[19
]}

Spagnolo, Francesco ^{[19
]}

Cecchi, Federica ^{[19
]}

Bracarda, Sergio ^{[20
]}

Macrini, Serena ^{[20
]}

Santoni, Matteo ^{[21
]}

Battelli, Nicola ^{[21
]}

Fargnoli, Maria Concetta ^{[22
,23
]}

Porzio, Giampiero ^{[22
,24
]}

Tuzi, Alessandro ^{[1
]}

Suter, Matteo Basilio ^{[1
]}

Ficorella, Corrado ^{[22
,24
]}

机构：

[1] Osped Circolo & Fdn Macchi, ASST Sette Laghi, Med Oncol, Varese, Italy

[2] IDI IRCCS, Oncol & Oncol Dermatol, Rome, Italy

[3] Azienda Osped Univ St Andrea, Med Oncol, Rome, Italy

[4] Azienda Osped Univ Parma, Med Oncol, Parma, Italy

[5] IRCCS Ist Tumori Giovanni Paolo II, Thorac Oncol Unit, Bari, Italy

[6] Univ Roma La Sapienza, Dipartimento Sci Med Chirurg & Med Traslaz, Rome, Italy

[7] Med Oncol, Campus Biomed, Rome, Italy

[8] Univ Politecn Marche, Clin Oncol, Azienda Osped Univ Osped Riuniti Umberto 1, GM Lancisi, Ancona, Italy

[9] Univ Perugia, Dept Surg & Biomed Sci, Perugia, Italy

[10] Osped Riuniti Padova Sud Madre Teresa Di Calcutta, Med Oncol, Monselice, Italy

[11] Univ Messina, AO Papardo & Dept Human Pathol, Med Oncol, Messina, Italy

[12] ASUR Marche, Area Vasta 2, Med Oncol, Fabriano, Italy

[13] Osped St Anna, ASST Lariana, Med Oncol, Como, Italy

[14] SS Annunziata Hosp, Clin Oncol Unit, Chieti, Italy

[15] Univ G DAnnunzio, Dept Med Oral & Biotechnol Sci, Chieti, Italy

[16] Osped Maggiore Policlin, Fdn IRCCS Ca Granda, Med Oncol Unit, Milan, Italy

[17] Univ Bari, Med Oncol Unit, Dept Biomed Sci & Human Oncol, Bari, Italy

[18] IRCCS, European Inst Oncol, Div Med Oncol Melanoma Sarcoma & Rare Tumors, IEO, Milan, Italy

[19] Osped Policlin San Martino, IRCCS, Genoa, Italy

[20] Santa Maria Hosp, Dept Med Oncol, Terni, Italy

[21] Macerata Hosp, Dept Oncol, Macerata, Italy

[22] St Salvatore Hosp, Dept Dermatol, Laquila, Italy

[23] Univ Aquila, Dept Biotechnol & Appl Clin Sci, Laquila, Italy

[24] St Salvatore Hosp, Med Oncol, Laquila, Italy

[25] Tumori Inst Giovanni Paolo II, Natl Canc Res Ctr, Bari, Italy

来源：

EUROPEAN JOURNAL OF CANCER | 2020年 / 134卷

关键词：

Immunotherapy; Immune checkpoint; Nivolumab; Pembrolizumab; Atezolizumab; Immune-related adverse events; ELDERLY-PATIENTS; CANCER;

D O I：

10.1016/j.ejca.2020.04.025

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background: Data on spectrum and grade of immune-related adverse events (irAEs) in long-term responders to immune checkpoint inhibitors (ICIs) are lacking. Methods: We performed a retrospective multicenter study to characterized irAEs occurring after a 12-months minimum treatment period with PD-(L)1 ICIs in patients with advanced cancer. IrAEs were categorized into 'early' (<= 12 months) and 'late' (>12 months). Results: From September 2013 to October 2019, 436 consecutive patients were evaluated. Two hundred twenty-three experienced any grade early-irAEs (51.1%), whereas 132 experienced any grade late-irAEs (30.3%) (p < 0.0001). Among the latter, 29 (22%) experienced a recurrence of an early-irAEs, whereas 103 (78%) experienced de novo late-irAEs involving different system/organ. Among patients with late-irAEs, 21 experienced GIII/GIV irAEs (4.8%). Median time to onset of early-irAEs was 3.4 months (95% confidence interval [CI]: 2.8-4.2), whereas the median time to onset of late-irAEs was 16.6 months (95% CI: 15.8-17.6). Cumulative time-adjusted risk of disease progression according to both the early-irAEs (hazard ratio [HR] = 0.63 [95% CI: 0.30-1.29], p = 0.204) and late-irAEs occurrence revealed no statistically significant differences (HR = 0.75 [95% CI: 0.37-1.56], p = 0.452). In addition, the time-adjusted cumulative risk of death in accordance with both early-irAEs (HR = 0.79 [95% CI: 0.34-1.86], p = 0.598) and late-irAEs (HR = 0.92 [95% CI: 0.49-1.74], p = 0.811) did not show statistically significant differences. Conclusion: Although less frequent than early-irAEs, late-irAEs are quite common in long responders to PD-(L)1 ICIs and are different in terms of spectrum and grade. Time-adjusted analysis revealed that the cumulative risk of disease progression and death were not significantly reduced in patients who experienced late-irAEs. (C) 2020 Elsevier Ltd. All rights reserved.

引用

页码：19 / 28

页数：10

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