PMID- 35710293
OWN - NLM
STAT- MEDLINE
DCOM- 20220620
LR  - 20220716
IS  - 2051-1426 (Electronic)
IS  - 2051-1426 (Linking)
VI  - 10
IP  - 6
DP  - 2022 Jun
TI  - Integrated use of PD-1 inhibition and transarterial chemoembolization for 
      hepatocellular carcinoma: evaluation of safety and efficacy in a retrospective, 
      propensity score-matched study.
LID - 10.1136/jitc-2021-004205 [doi]
LID - e004205
AB  - BACKGROUND: Immune checkpoint inhibitors (ICIs) have revolutionized treatment of 
      advanced hepatocellular carcinoma. Integrated use of transarterial 
      chemoembolization (TACE), a locoregional inducer of immunogenic cell death, with 
      ICI has not been formally assessed for safety and efficacy outcomes. METHODS: 
      From a retrospective multicenter dataset of 323 patients treated with ICI, we 
      identified 31 patients who underwent >1 TACE 60 days before or concurrently, with 
      nivolumab at a single center. We derived a propensity score-matched cohort of 104 
      patients based on Child-Pugh Score, portal vein thrombosis, extrahepatic 
      metastasis and alpha fetoprotein (AFP) who received nivolumab monotherapy. We 
      described overall survival (OS), progression-free survival (PFS), objective 
      responses according to modified RECIST criteria and safety in the multimodal arm 
      in comparison to monotherapy. RESULTS: Over a median follow-up of 9.3 (IQR 
      4.0-16.4) months, patients undergoing multimodal immunotherapy with TACE achieved 
      a significantly longer median (95% CI) PFS of 8.8 (6.2-23.2) vs 3.7 (2.7-5.4) 
      months (log-rank 0.15, p<0.01) in the monotherapy group. Multimodal immunotherapy 
      with TACE demonstrated a numerically longer OS compared with ICI monotherapy with 
      a median 35.1 (16.1-Not Evaluable) vs 16.6 (15.7-32.6) months (log-rank 0.41, 
      p=0.12). In the multimodal treatment group, there were three (10%) grade 3 or 
      higher adverse events (AEs) attributed to immunotherapy compared with seven 
      (6.7%) in the matched ICI monotherapy arm. There were no AEs grade 3 or higher 
      attributed to TACE in the multimodal treatment arm. At 3 months following each 
      TACE in the multimodal arm, there was an overall objective response rate of 84%. 
      There were no significant changes in liver functional reserve 1 month following 
      each TACE. Four patients undergoing multimodal treatment were successfully 
      bridged to transplant. CONCLUSIONS: TACE can be safely integrated with programmed 
      cell death 1 blockade and may lead to a significant delay in tumor progression 
      and disease downstaging in selected patients.
CI  - (c) Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No 
      commercial re-use. See rights and permissions. Published by BMJ.
FAU - Marinelli, Brett
AU  - Marinelli B
AUID- ORCID: 0000-0003-3220-1360
AD  - Division of Interventional Radiology, Icahn School of Medicine at Mount Sinai, 
      New York City, New York, USA.
FAU - Kim, Edward
AU  - Kim E
AD  - Division of Interventional Radiology, Icahn School of Medicine at Mount Sinai, 
      New York City, New York, USA.
FAU - D'Alessio, Antonio
AU  - D'Alessio A
AD  - Department of Surgery and Cancer, Imperial College London, London, UK.
FAU - Cedillo, Mario
AU  - Cedillo M
AD  - Division of Interventional Radiology, Icahn School of Medicine at Mount Sinai, 
      New York City, New York, USA.
FAU - Sinha, Ishan
AU  - Sinha I
AD  - Division of Interventional Radiology, Icahn School of Medicine at Mount Sinai, 
      New York City, New York, USA.
FAU - Debnath, Neha
AU  - Debnath N
AD  - Division of Hematology and Oncology, Icahn School of Medicine at Mount Sinai, New 
      York City, New York, USA.
FAU - Kudo, Masatoshi
AU  - Kudo M
AD  - Faculty of Medicine Hospital, Department of Gastroenterology and Hepatology, 
      Kindai University, Osakasayama, Japan.
FAU - Nishida, Naoshi
AU  - Nishida N
AD  - Faculty of Medicine Hospital, Department of Gastroenterology and Hepatology, 
      Kindai University, Osakasayama, Japan.
FAU - Saeed, Anwaar
AU  - Saeed A
AD  - Department of Medicine, Division of Clinical Oncology, University of Kansas 
      Medical Center, Kansas City, Kansas, USA.
FAU - Hildebrand, Hannah
AU  - Hildebrand H
AD  - Department of Medicine, Division of Clinical Oncology, University of Kansas 
      Medical Center, Kansas City, Kansas, USA.
FAU - Kaseb, Ahmed O
AU  - Kaseb AO
AD  - Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, 
      University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
FAU - Abugabal, Yehia I
AU  - Abugabal YI
AD  - Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, 
      University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
FAU - Pillai, Anjana
AU  - Pillai A
AD  - Department of Medicine, Section of Gastroenterology, University of Chicago, 
      Chicago, Illinois, USA.
FAU - Huang, Yi-Hsiang
AU  - Huang YH
AUID- ORCID: 0000-0001-5241-5425
AD  - Division of Gastroenterology and Hepatology, Taipei Veterans General Hospital, 
      Taipei, Taiwan.
AD  - Institute of Clinical Medicine, National Yang Ming Chiao Tung University School 
      of Medicine, Taipei, Taiwan.
FAU - Khan, Uqba
AU  - Khan U
AD  - Division of Hematology and Medical Oncology, Weill Cornell Medicine, New York 
      City, New York, USA.
FAU - Muzaffar, Mahvish
AU  - Muzaffar M
AD  - Department of Medicine, Division of Hematology and Oncology, Brody School of 
      Medicine at East Carolina University, Greenville, North Carolina, USA.
FAU - Naqash, Abdul Rafeh
AU  - Naqash AR
AUID- ORCID: 0000-0001-7622-720X
AD  - Department of Medicine, Division of Hematology and Oncology, Stephenson Cancer 
      Center at the University of Oklahoma, Oklahoma City, Oklahoma, USA.
FAU - Patel, Rahul
AU  - Patel R
AD  - Division of Interventional Radiology, Icahn School of Medicine at Mount Sinai, 
      New York City, New York, USA.
FAU - Fischman, Aaron
AU  - Fischman A
AD  - Division of Interventional Radiology, Icahn School of Medicine at Mount Sinai, 
      New York City, New York, USA.
FAU - Bishay, Vivian
AU  - Bishay V
AD  - Division of Interventional Radiology, Icahn School of Medicine at Mount Sinai, 
      New York City, New York, USA.
FAU - Bettinger, Dominik
AU  - Bettinger D
AD  - Department of Medicine II, University of Freiburg Medical Center, Freiburg, 
      Germany.
FAU - Sung, Max
AU  - Sung M
AD  - Division of Hematology and Oncology, Icahn School of Medicine at Mount Sinai, New 
      York City, New York, USA.
FAU - Ang, Celina
AU  - Ang C
AD  - Hematology and Oncology, Mount Sinai School of Medicine, New York City, New York, 
      USA.
FAU - Schwartz, Myron
AU  - Schwartz M
AD  - Department of Surgery, Recanti/Miller Transplant Institute at the Icahn School of 
      Medicine at Mount Sinai, New York City, New York, USA.
FAU - Pinato, David J
AU  - Pinato DJ
AUID- ORCID: 0000-0002-3529-0103
AD  - Department of Surgery and Cancer, Imperial College London, London, UK.
FAU - Marron, Thomas
AU  - Marron T
AD  - Division of Hematology and Medical Oncology, Mount Sinai School of Medicine, New 
      York City, New York, USA thomas.marron@mountsinai.org.
LA  - eng
PT  - Journal Article
PT  - Multicenter Study
PL  - England
TA  - J Immunother Cancer
JT  - Journal for immunotherapy of cancer
JID - 101620585
RN  - 0 (Programmed Cell Death 1 Receptor)
RN  - 31YO63LBSN (Nivolumab)
SB  - IM
MH  - *Carcinoma, Hepatocellular/drug therapy
MH  - *Chemoembolization, Therapeutic/adverse effects
MH  - Humans
MH  - *Liver Neoplasms/pathology
MH  - Nivolumab/therapeutic use
MH  - Programmed Cell Death 1 Receptor
MH  - Propensity Score
MH  - Retrospective Studies
MH  - Treatment Outcome
PMC - PMC9204420
OTO - NOTNLM
OT  - Combined Modality Therapy
OT  - Immunomodulation
OT  - Liver Neoplasms
COIS- Competing interests: EK is a consultant for Koninklijke Philips Electronics 
      (Amsterdam, Netherlands) and is on the advisory board for Onyx Pharmaceuticals 
      (South San Francisco, California) and the speaker's bureau for BTG International 
      (West Conshohocken, Pennsylvania). RP is a consultant for Sirtex Medical (North 
      Sydney, Australia) and Arstasis (Fremont, California). AF is a consultant for 
      Surefire Medical (Westminster, Colorado) and Terumo Medical Corporation 
      (Somerset, New Jersey) and is on the advisory board for Terumo Medical 
      Corporation. DB is a consultant for Bayer Healthcare, Boston Scientific and 
      Shionogi and lecturer for Falk Foundation. YH has research grants from Gilead 
      Sciences and Bristol Myers Squibb and honoraria from Abbvie, Gilead Sciences, 
      Bristol Myers Squibb, Ono Pharmaceutical, Merck Sharp & Dohme, Eisai, Eli Lilly, 
      Ipsen and Roche, and serves as advisor for Abbvie, Gilead Sciences, Bristol Myers 
      Squibb, Ono Pharmaceuticals, Eisai, Eli Lilly, Ipsen, Merck Sharp & Dohme and 
      Roche. AS has research grants from AstraZeneca, Merck, Bristol Myers Squibb, 
      Exelixis and Clovis and receives advisory board/consultant fees from AstraZeneca, 
      Merck, Bristol Myers Squibb, Exelixis and Pfizer. AP is on the medical advisory 
      board for Exelixis, Eisai, AstraZeneca and Genentech, safety review committee for 
      Replimune and on the speaking bureau for Simply Speaking Hepatitis. MK is a 
      consultant for Eisai, Ono Pharmaceutical Co, Merck Sharpe & Dohme Corp, Bristol 
      Meyer Squibb and Roche; research contracts grants from Ono Pharmaceutical Co; 
      grants from Eisai, Takeda, Otsuka, Taiho, EQ pharma, Gilead Sciences, Abbvie, 
      Sumitomo Dainippon Pharma, Chugai, Ono Pharmaceutical; and is an honorary 
      lecturer for Eisai, Bayer, Merck Sharpe & Dohme Corp, Bristol Meyer Squibb, EA 
      Pharma, Eli Lilly and Chugai. TUM has served as an advisor and/or data-safety 
      boards for Regeneron, Boehringer Ingelheim, Atara, Genentech, AstraZeneca, 
      Chimeric Therapeutics, Riboscience, Celldex and Rockefeller University, and has 
      research grants from Regeneron, Bristol-Myers Squibb and Boehringer Ingelheim. 
      None of the other authors have identified a conflict of interest.
EDAT- 2022/06/17 06:00
MHDA- 2022/06/22 06:00
PMCR- 2022/06/16
CRDT- 2022/06/16 21:11
PHST- 2022/05/13 00:00 [accepted]
PHST- 2022/06/16 21:11 [entrez]
PHST- 2022/06/17 06:00 [pubmed]
PHST- 2022/06/22 06:00 [medline]
PHST- 2022/06/16 00:00 [pmc-release]
AID - jitc-2021-004205 [pii]
AID - 10.1136/jitc-2021-004205 [doi]
PST - ppublish
SO  - J Immunother Cancer. 2022 Jun;10(6):e004205. doi: 10.1136/jitc-2021-004205.