Clinical outcomes and safety of immune checkpoint inhibitors in patients with solid tumors and paraneoplastic syndromes

被引：2

作者：

Nassar, Amin H. ^{[1
]}

El Zarif, Talal ^{[1
,2
,3
]}

Khalid, Ahmed Bilal ^{[4
]}

Rahme, Serena ^{[5
]}

Zhong, Caiwei ^{[3
]}

Kwak, Lucia ^{[3
]}

Salame, Marita ^{[6
]}

Farhat, Elias Bou ^{[3
]}

Freeman, Dory ^{[3
]}

El-Am, Edward ^{[6
]}

Ravishankar, Arjun ^{[1
,2
]}

Ahmad, Bachar ^{[1
,2
]}

Nana, Frank Aboubakar ^{[7
,8
]}

Kaldas, David ^{[9
,10
]}

Naqash, Abdul Rafeh ^{[11
]}

Sharon, Elad ^{[12
]}

LeBoeuf, Nicole R. ^{[13
]}

Cortellini, Alessio ^{[14
,15
]}

Malgeri, Andrea ^{[14
]}

Gupta, Shruti ^{[16
]}

Al-Hader, Ahmad ^{[4
]}

Sparks, Jeffrey A. ^{[13
]}

Linnoila, Jenny ^{[17
]}

Hamnvik, Ole-Petter R. ^{[13
]}

Mouhieddine, Tarek H. ^{[18
]}

Marron, Thomas ^{[19
]}

Parikh, Kaushal ^{[6
]}

McKay, Rana R. ^{[20
]}

Dilling, Thomas ^{[9
]}

Choueiri, Toni K. ^{[21
]}

Adib, Elio ^{[13
]}

Najem, Elie ^{[22
]}

Kim, So Yeon ^{[1
]}

Sonpavde, Guru ^{[23
,24
]}

机构：

[1] Yale Univ, New Haven, CT 06520 USA

[2] Yale Univ, Sch Med, New Haven, CT USA

[3] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA

[4] Indiana Melvin & Bren Simon Comprehens Canc Ctr, Indianapolis, IN USA

[5] Dept Cardiovasc Med, Mayo Clin, Rochester, NY USA

[6] Mayo Clin, Rochester, MN USA

[7] CHU UCL Namur, Div Pulmonol, Namur, Belgium

[8] Div Pneumol, Clin Univ St Luc, Brussels, Belgium

[9] Univ S Florida, Dept Internal Med, Tampa, FL USA

[10] Cairo Univ, Dept Clin Oncol, Giza, Egypt

[11] Univ Oklahoma, Stephenson Canc Ctr, Med Oncol TSET Phase 1 Program, Oklahoma City, OK USA

[12] NCI, Bethesda, MD USA

[13] Harvard Med Sch, Boston, MA USA

[14] Fdn Policlin Univ Campus Biomed, Med Oncol, Rome, Italy

[15] Univ Campus Biomed Roma, Dept Med & Surg, Rome, Italy

[16] Brigham & Womens Hosp, Boston, MA USA

[17] Massachusetts Gen Hosp, Boston, MA USA

[18] Icahn Sch Med Mt Sinai, New York, NY USA

[19] Icahn Sch Med Mt Sinai, Oncol, New York, NY USA

[20] Univ Calif San Diego, Div Med Oncol, La Jolla, CA 92093 USA

[21] Dana Farber Canc Inst, Med Oncol, Boston, MA USA

[22] Harvard Med Sch, Dept Radiol, Boston, MA USA

[23] AdventHlth Cent Florida, AdventHealth Cent Florida, Orlando, FL USA

[24] AdventHlth Canc Inst, AdventHealth, Altamonte Springs, FL USA

来源：

JOURNAL FOR IMMUNOTHERAPY OF CANCER | 2024年 / 12卷 / 03期

关键词：

PARANEOPLASTIC SYNDROME; Immune Checkpoint Inhibitors; Non-Small Cell Lung Cancer; NIVOLUMAB;

D O I：

10.1136/jitc-2023-008724

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background Patients with paraneoplastic syndromes (PNS) are excluded from clinical trials involving immune checkpoint inhibitors (ICIs) due to safety concerns. Moreover, real-world data on efficacy and safety is scarce.Methods In this retrospective study, data were collected on patients with PNS and solid tumors receiving ICI between 2015 and 2022 at nine institutions. Patients were classified into: Cohort 1 (pre-existing PNS before ICI initiation), cohort 2 (PNS during ICI treatment), and cohort 3 (PNS after ICI discontinuation). Patients with metastatic non-small cell lung cancer (NSCLC) (mNSCLC) from cohort 1 were matched to patients who were PNS-free at each institution up to a 1:3 ratio for age, sex, type of ICI, use of concurrent chemotherapy, and number of lines of systemic therapy prior to ICI initiation. Kaplan-Meier method was used to assess overall survival (OS) and time-to-next treatment (TTNT).Results Among 109 patients with PNS treated with ICIs, median age at ICI initiation was 67 years (IQR: 58-74). The most represented cancer type was NSCLC (n=39, 36%). In cohort 1 (n=55), PNS exacerbations occurred in 16 (29%) patients with median time to exacerbation after ICI of 1.1 months (IQR: 0.7-3.3). Exacerbation or de novo PNS prompted temporary/permanent interruption of ICIs in 14 (13%) patients. For cohort 2 (n=16), median time between ICI initiation and de novo PNS was 1.2 months (IQR: 0.4-3.5). Treatment-related adverse events (trAEs) occurred in 43 (39%) patients. Grade >= 3 trAEs occurred in 18 (17%) patients. PNS-directed immunosuppressive therapy was required in 55 (50%) patients. We matched 18 patients with mNSCLC and PNS (cohort 1) to 40 without PNS, treated with ICIs. There was no significant difference in OS or TTNT between patients with mNSCLC with and without PNS, although a trend was seen towards worse outcomes in patients with PNS. TrAEs occurred in 6/18 (33%) and 14/40 (35%), respectively. Grade >= 3 trAEs occurred in 4 (22%) patients with PNS and 7 (18%) patients without PNS.Conclusions Exacerbations of pre-existing PNS occurred in 29% of patients treated with ICIs and both exacerbations and de novo PNS occur early in the ICI course. TrAE from ICIs were similar between patients with and without PNS. Our data suggest that pre-existing PNS should not preclude consideration of ICI therapy although patients may not derive the same clinical benefit compared with patients without PNS.

引用

页数：11

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