PMID- 38448038
OWN - NLM
STAT- MEDLINE
DCOM- 20240308
LR  - 20240312
IS  - 2051-1426 (Electronic)
IS  - 2051-1426 (Linking)
VI  - 12
IP  - 3
DP  - 2024 Mar 5
TI  - Clinical outcomes and safety of immune checkpoint inhibitors in patients with 
      solid tumors and paraneoplastic syndromes.
LID - 10.1136/jitc-2023-008724 [doi]
LID - e008724
AB  - 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.
CI  - (c) Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No 
      commercial re-use. See rights and permissions. Published by BMJ.
FAU - Nassar, Amin H
AU  - Nassar AH
AUID- ORCID: 0000-0002-4507-2396
AD  - Yale University, New Haven, Connecticut, USA amin.nassar@yale.edu.
FAU - El Zarif, Talal
AU  - El Zarif T
AD  - Yale University, New Haven, Connecticut, USA.
AD  - Yale University School of Medicine, New Haven, Connecticut, USA.
AD  - Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, 
      Massachusetts, USA.
FAU - Khalid, Ahmed Bilal
AU  - Khalid AB
AD  - Indiana Melvin and Bren Simon Comprehensive Cancer Center, Indianapolis, Indiana, 
      USA.
FAU - Rahme, Serena
AU  - Rahme S
AD  - Department of Cardiovascular Medicine, Mayo Clinic, Rochester, New York, USA.
FAU - Zhong, Caiwei
AU  - Zhong C
AD  - Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, 
      Massachusetts, USA.
FAU - Kwak, Lucia
AU  - Kwak L
AD  - Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, 
      Massachusetts, USA.
FAU - Salame, Marita
AU  - Salame M
AD  - Mayo Clinic, Rochester, Minnesota, USA.
FAU - Farhat, Elias Bou
AU  - Farhat EB
AD  - Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, 
      Massachusetts, USA.
FAU - Freeman, Dory
AU  - Freeman D
AD  - Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, 
      Massachusetts, USA.
FAU - El-Am, Edward
AU  - El-Am E
AD  - Mayo Clinic, Rochester, Minnesota, USA.
FAU - Ravishankar, Arjun
AU  - Ravishankar A
AD  - Yale University, New Haven, Connecticut, USA.
AD  - Yale University School of Medicine, New Haven, Connecticut, USA.
FAU - Ahmad, Bachar
AU  - Ahmad B
AD  - Yale University, New Haven, Connecticut, USA.
AD  - Yale University School of Medicine, New Haven, Connecticut, USA.
FAU - Nana, Frank Aboubakar
AU  - Nana FA
AD  - Division of Pneumology, CHU UCL Namur, Yvoir, Namur, Belgium.
AD  - Division of Pneumology, Cliniques universitaires Saint-Luc, Brussels, Belgium.
FAU - Kaldas, David
AU  - Kaldas D
AD  - Department of Internal Medicine, University of South Florida, Tampa, Florida, 
      USA.
AD  - Department of Clinical Oncology, Cairo University, Giza, Egypt.
FAU - Naqash, Abdul Rafeh
AU  - Naqash AR
AD  - Medical Oncology/TSET Phase 1 Program, The University of Oklahoma Stephenson 
      Cancer Center, Oklahoma City, Oklahoma, USA.
FAU - Sharon, Elad
AU  - Sharon E
AD  - National Cancer Institute, Bethesda, Maryland, USA.
FAU - LeBoeuf, Nicole R
AU  - LeBoeuf NR
AD  - Harvard Medical School, Boston, Massachusetts, USA.
FAU - Cortellini, Alessio
AU  - Cortellini A
AD  - Medical Oncology, Fondazione Policlinico Universitario Campus Bio-Medico, Rome, 
      Italy.
AD  - Department of Medicine and Surgery, Universita Campus Bio-Medico di Roma, Rome, 
      Italy.
FAU - Malgeri, Andrea
AU  - Malgeri A
AD  - Medical Oncology, Fondazione Policlinico Universitario Campus Bio-Medico, Rome, 
      Italy.
FAU - Gupta, Shruti
AU  - Gupta S
AUID- ORCID: 0000-0002-5747-2151
AD  - Brigham and Women's Hospital, Boston, Massachusetts, USA.
FAU - Al-Hader, Ahmad
AU  - Al-Hader A
AD  - Indiana Melvin and Bren Simon Comprehensive Cancer Center, Indianapolis, Indiana, 
      USA.
FAU - Sparks, Jeffrey A
AU  - Sparks JA
AD  - Harvard Medical School, Boston, Massachusetts, USA.
FAU - Linnoila, Jenny
AU  - Linnoila J
AD  - Massachusetts General Hospital, Boston, Massachusetts, USA.
FAU - Hamnvik, Ole-Petter R
AU  - Hamnvik OR
AD  - Harvard Medical School, Boston, Massachusetts, USA.
FAU - Mouhieddine, Tarek H
AU  - Mouhieddine TH
AD  - Icahn School of Medicine at Mount Sinai, New York, New York, USA.
FAU - Marron, Thomas
AU  - Marron T
AUID- ORCID: 0000-0001-5903-8191
AD  - Oncology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
FAU - Parikh, Kaushal
AU  - Parikh K
AD  - Mayo Clinic, Rochester, Minnesota, USA.
FAU - McKay, Rana R
AU  - McKay RR
AD  - Division of Medical Oncology, University of California San Diego, La Jolla, 
      California, USA.
FAU - Dilling, Thomas
AU  - Dilling T
AD  - Department of Internal Medicine, University of South Florida, Tampa, Florida, 
      USA.
FAU - Choueiri, Toni K
AU  - Choueiri TK
AUID- ORCID: 0000-0002-9201-3217
AD  - Medical Oncology, Dana Farber Cancer Institute, Boston, Massachusetts, UK.
FAU - Adib, Elio
AU  - Adib E
AUID- ORCID: 0000-0003-0594-7976
AD  - Harvard Medical School, Boston, Massachusetts, USA.
FAU - Najem, Elie
AU  - Najem E
AD  - Department of Radiology, Harvard Medical School, Boston, Massachusetts, USA.
FAU - Kim, So Yeon
AU  - Kim SY
AUID- ORCID: 0000-0003-4102-5880
AD  - Yale University, New Haven, Connecticut, USA.
FAU - Sonpavde, Guru
AU  - Sonpavde G
AUID- ORCID: 0000-0002-1010-9611
AD  - Medical Oncology, AdventHealth Central Florida, Orlando, Florida, USA.
AD  - AdventHealth Cancer Institute, AdventHealth, Altamonte Springs, Florida, USA.
LA  - eng
GR  - R01 AR077607/AR/NIAMS NIH HHS/United States
GR  - P30 AR072577/AR/NIAMS NIH HHS/United States
GR  - UL1 TR001863/TR/NCATS NIH HHS/United States
GR  - P30 AR070253/AR/NIAMS NIH HHS/United States
GR  - R01 AR080659/AR/NIAMS NIH HHS/United States
PT  - Journal Article
DEP - 20240305
PL  - England
TA  - J Immunother Cancer
JT  - Journal for immunotherapy of cancer
JID - 101620585
RN  - 0 (Immune Checkpoint Inhibitors)
SB  - IM
MH  - Humans
MH  - Middle Aged
MH  - Aged
MH  - Immune Checkpoint Inhibitors/adverse effects
MH  - *Carcinoma, Non-Small-Cell Lung/drug therapy
MH  - Retrospective Studies
MH  - *Lung Neoplasms/drug therapy
MH  - *Paraneoplastic Syndromes/drug therapy/etiology
PMC - PMC10916116
OTO - NOTNLM
OT  - Immune Checkpoint Inhibitors
OT  - Non-Small Cell Lung Cancer
OT  - PARANEOPLASTIC SYNDROME
COIS- Competing interests: AHN receives honoraria from OncLive, TEMPUS, and Korean 
      Society for Medical Oncology. Consulting fees: Guidepoint Global. RRM: 
      Consulting/Advisory Board - Aveo, AstraZeneca, Bayer, Bristol Myers Squibb, Blue 
      Earth Diagnostics, Calithera, Caris, Denderon, Exelixis, Janssen, Merck, Myovant, 
      Pfizer, Sanofi, SeaGen, Sorrento Therapeutics, Tempus. Institutional Research 
      Funding - AstraZeneca, BMS, Exelixis, Artera, Oncternal, Bayer, Tempus. JAS is 
      supported by the National Institute of Arthritis and Musculoskeletal and Skin 
      Diseases (grant numbers R01 AR080659, R01 AR077607, P30 AR070253, and P30 
      AR072577), the R. Bruce and Joan M. Mickey Research Scholar Fund, and the Llura 
      Gund Award funded by the Gordon and Llura Gund Foundation. JAS has received 
      research support from Bristol Myers Squibb and performed consultancy for AbbVie, 
      Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Gilead, Inova Diagnostics, 
      Janssen, Optum, Pfizer, ReCor, and Sobi unrelated to this work. The funders had 
      no role in the decision to publish or preparation of this manuscript. The content 
      is solely the responsibility of the authors and does not necessarily represent 
      the official views of Harvard University, its affiliated academic health care 
      centers, or the National Institutes of Health. AC received grants for 
      consultancies/advisory boards: MSD, OncoC4, IQVIA, AstraZeneca, Access Infinity, 
      Ardelis Health, Alpha Sight. Speaker fees: AstraZeneca, Eisai, Pierre-Fabre, MSD. 
      Writing/Editorial activity: BMS. Travel support: Sanofi and MSD. ARN reports 
      Funding to Institution for Trials he is PI on:Loxo@Lilly, Surface Oncology, ADC 
      Therapeutics, IGM Biosciences, EMD Serono, Aravive, Nikang Therapeutics, 
      Inspirna, Exelixis, Revolution Medicine, Jacobio, Pionyr, Jazz Pharmaceuticals, 
      NGM Biopharmaceuticals. ARN receives Consultant Editor Compensation: JCO 
      Precision Oncology. Consulting/Advisory Board: Foundation Med. ARN reports Travel 
      Compensation from: SITC/ AACR/ Conquer Cancer Foundation, Jazz Pharmaceuticals, 
      Binay Tara Foundation, Foundation Med.
EDAT- 2024/03/07 00:42
MHDA- 2024/03/08 06:43
PMCR- 2024/03/05
CRDT- 2024/03/06 20:43
PHST- 2024/02/05 00:00 [accepted]
PHST- 2024/03/08 06:43 [medline]
PHST- 2024/03/07 00:42 [pubmed]
PHST- 2024/03/06 20:43 [entrez]
PHST- 2024/03/05 00:00 [pmc-release]
AID - jitc-2023-008724 [pii]
AID - 10.1136/jitc-2023-008724 [doi]
PST - epublish
SO  - J Immunother Cancer. 2024 Mar 5;12(3):e008724. doi: 10.1136/jitc-2023-008724.