PMID- 34153388
OWN - NLM
STAT- MEDLINE
DCOM- 20220414
LR  - 20220414
IS  - 1097-6787 (Electronic)
IS  - 0190-9622 (Linking)
VI  - 86
IP  - 2
DP  - 2022 Feb
TI  - Late-onset adverse events of anti-PD1 therapy in melanoma patients: An 
      observational study from MELBASE, a nationwide prospective cohort.
PG  - 345-352
LID - S0190-9622(21)01991-5 [pii]
LID - 10.1016/j.jaad.2021.06.849 [doi]
AB  - BACKGROUND: Late-onset adverse events (AEs) of anti-programmed cell death 1 
      (anti-PD1) antibodies have not been systematically described. OBJECTIVES: The 
      purpose was to evaluate late-onset AEs in melanoma patients treated with anti-PD1 
      administered for at least 2 years in a real-life setting. METHODS: Patients were 
      screened from MelBase, a French multicentric biobank dedicated to the prospective 
      follow up of unresectable stage III or IV melanoma. The study included 119 
      patients who received anti-PD1 during at least 2 years from January 2013 to 
      November 2019. Median follow up was 41.7 months (range, 25.2-57.5 months). 
      Fifty-three patients received nivolumab and 66 patients received pembrolizumab. 
      RESULTS: AEs occurred in 99 patients (83%) with a median time of 13.3 months 
      (range, 0-53.9 months), including severe AEs (grade 3 or 4) in 30 patients (30%). 
      Late-onset AEs, mostly grades 1 or 2, occurred in 51 (43%) patients and led to 5 
      (4%) hospitalizations, of which 4 were severe. Factors associated with late-onset 
      AEs in multivariate analysis were early-onset AEs (within the first 2 years of 
      treatment) and treatment duration (P = .02 and P = .03, respectively). 
      CONCLUSIONS: Our data demonstrate the possibility of late-onset AEs occurring 
      after 2 years of anti-PD1 therapy. Late-onset AEs appear frequently and were 
      mostly mild or moderate. Early-onset AEs and prolonged anti-PD1 treatment may 
      increase the risk of late-onset AEs.
CI  - Copyright (c) 2021. Published by Elsevier Inc.
FAU - Carlet, Clementine
AU  - Carlet C
AD  - Service de Dermatologie, Centre Hospitalier Universitaire and Unite mixte de 
      recherche 1098, Besancon, France.
FAU - Dalle, Stephane
AU  - Dalle S
AD  - Hospices Civils de Lyon, Immucare, Centre de Recherche en Cancerologie de Lyon, 
      Lyon, France.
FAU - Leccia, Marie-Therese
AU  - Leccia MT
AD  - Centre Hospitalier Universitaire, Grenoble, France.
FAU - Mortier, Laurent
AU  - Mortier L
AD  - Centre Hospitalier Universitaire, Lille, France.
FAU - Dalac-Rat, Sophie
AU  - Dalac-Rat S
AD  - Centre Hospitalier Universitaire, Dijon, France.
FAU - Dutriaux, Caroline
AU  - Dutriaux C
AD  - Centre Hospitalier Universitaire, Bordeaux, France.
FAU - Legoupil, Delphine
AU  - Legoupil D
AD  - Centre Hospitalier Universitaire, Brest, France.
FAU - Montaudie, Henri
AU  - Montaudie H
AD  - Centre Hospitalier Universitaire, Nice, and INSERM U1065, Centre Mediterraneen de 
      Medecine Moleculaire, Nice, France.
FAU - Dereure, Olivier
AU  - Dereure O
AD  - Centre Hospitalier Universitaire, Montpellier, France.
FAU - De Quatrebarbes, Julie
AU  - De Quatrebarbes J
AD  - Centre Hospitalier, Annecy, France.
FAU - Granel-Brocard, Florence
AU  - Granel-Brocard F
AD  - Centre Hospitalier Universitaire, Nancy, Vandoeuvre-Les-Nancy, Nancy, France.
FAU - Le-Bouar, Myrtille
AU  - Le-Bouar M
AD  - Hospices Civils de Lyon, Immucare, Centre de Recherche en Cancerologie de Lyon, 
      Lyon, France.
FAU - Charles, Julie
AU  - Charles J
AD  - Centre Hospitalier Universitaire, Grenoble, France.
FAU - Brunet-Possenti, Florence
AU  - Brunet-Possenti F
AD  - Centre Hospitalier Universitaire, Bichat-Claude Bernard, Paris France.
FAU - Dreno, Brigitte
AU  - Dreno B
AD  - Centre Hospitalier Universitaire, Nantes, France.
FAU - Lefevre, Wendy
AU  - Lefevre W
AD  - Centre Hospitalier Universitaire Saint Louis et Centre d'investigation clinique, 
      U976, Paris, France.
FAU - Allayous, Clara
AU  - Allayous C
AD  - Centre Hospitalier Universitaire Saint Louis et Centre d'investigation clinique, 
      U976, Paris, France.
FAU - Lebbe, Celeste
AU  - Lebbe C
AD  - Centre Hospitalier Universitaire Saint Louis et Centre d'investigation clinique, 
      U976, Paris, France.
FAU - Nardin, Charlee
AU  - Nardin C
AD  - Service de Dermatologie, Centre Hospitalier Universitaire and Unite mixte de 
      recherche 1098, Besancon, France. Electronic address: charleenardin@hotmail.fr.
LA  - eng
PT  - Journal Article
PT  - Observational Study
DEP - 20210618
PL  - United States
TA  - J Am Acad Dermatol
JT  - Journal of the American Academy of Dermatology
JID - 7907132
RN  - 31YO63LBSN (Nivolumab)
SB  - IM
MH  - Cohort Studies
MH  - Humans
MH  - Immunotherapy/adverse effects
MH  - *Melanoma/etiology
MH  - Nivolumab/adverse effects
MH  - Prospective Studies
MH  - Retrospective Studies
OTO - NOTNLM
OT  - adverse event
OT  - anti-PD1
OT  - immune checkpoint inhibitor
OT  - immunotherapy
OT  - late-onset adverse events
OT  - melanoma
OT  - nivolumab
OT  - pembrolizumab
OT  - toxicities
COIS- Conflicts of interest Dr Nardin has a Consulting or Advisory Role with 
      Bristol-Myers Squibb, MSD, Novartis, and reports travel, accommodations, and 
      expenses from Bristol-Myers Squibb, MSD, Novartis, and Pierre Fabre. Dr. Dalle is 
      an employee of Sanofi, has Stock and Other Ownership Interests in Sanofi, has a 
      Consulting or Advisory Role with Bristol-Myers Squibb, received Research Funding 
      from Bristol-Myers Squibb, and reports travel, accommodations, and expenses from 
      Bristol-Myers Squibb and Pierre Fabre. Dr Leccia has No Relationships to 
      Disclose. Dr Mortier received honoraria from Bristol-Myers Squibb and MSD 
      Oncology, received Research Funding from MSD Oncology and Pierre Fabre, and 
      received travel, accommodations, and expenses from Bristol-Myers Squibb, 
      Novartis, Roche/Genentech, and Roche/Genentech. Dr Dalac-Rat received honoraria 
      from Bristol-Myers Squibb, MSD, and Novartis, reports a Consulting or Advisory 
      Role with Bristol-Myers Squibb, MSD, and Novartis, is on the Speakers' Bureau for 
      Bristol-Myers Squibb, reports Research Funding from Bristol-Myers Squibb, MSD, 
      and Novartis, and reports travel, accommodations, and expenses from Bristol-Myers 
      Squibb. Dr Dutriaux received honoraria from Bristol-Myers Squibb, MSD, Novartis, 
      and Pierre Fabre reports a Consulting or Advisory Role with Bristol-Myers Squibb, 
      MSD, Novartis, and Pierre Fabre, and reports travel, accommodations, and expenses 
      from Bristol-Myers Squibb, MSD, Novartis, and Pierre Fabre. Dr Legoupil received 
      honoraria from Bristol-Myers Squibb and MSD, reports a Consulting or Advisory 
      Role with Bristol-Myers Squibb and Pierre Fabre, and reports travel, 
      accommodations, and expenses from Bristol-Myers Squibb, MSD, and Pierre Fabre. Dr 
      Montaudie reports a Consulting or Advisory Role with Bristol-Myers Squibb, MSD, 
      Novartis, and Pierre Fabre, received Research Funding from Leo Pharma and 
      Novartis, and reports travel, accommodations, and expenses from Bristol-Myers 
      Squibb, Novartis, and Pierre Fabre. Dr Dereure reports a Consulting or Advisory 
      Role with Bristol-Myers Squibb, Genevrier, Kiowa Kirin, Leo Pharma, MSD, 
      Novartis, Pierre Fabre, and Recordati, and reports travel, accommodations, and 
      expenses from Bristol-Myers Squibb, Novartis, Pierre Fabre, and Recordati. Dr De 
      Quatrebarbes is on the Speakers' Bureau for Bristol-Myers Squibb and 
      Janssen-Cilag and reports travel, accommodations, and expenses from BMS and MSD 
      Oncology. Dr Granel-Brocard has no relationships to disclose. Dr Le-Bouar has no 
      relationships to disclose. Dr Charles has no relationships to disclose. Dr 
      Brunet-Possenti reports a Consulting or Advisory Role with Bristol-Myers Squibb 
      and Sanofi. Dr Dreno received honoraria from Bristol-Myers Squibb, Merck, Pierre 
      Fabre, Roche, and Sanofi, reports a Consulting or Advisory Role with 
      Bristol-Myers Squibb, Pierre Fabre, Roche, and Sanofi, and reports travel, 
      accommodations, and expenses from Bristol-Myers Squibb, Pierre Fabre, and Roche. 
      Dr Lefevre has no relationships to disclose. Dr Allayous reports travel, 
      accommodations, and expenses from Amgen, Bristol-Myers Squibb, and Roche. Dr 
      Lebbe reports honoraria from Amgen, Bristol-Myers Squibb, Incyte, MSD, Novartis, 
      Pfizer, Pierre Fabre, and Roche, reports a Consulting or Advisory Role with 
      Amgen, Bristol-Myers Squibb, Merck Serono, MSD, Novartis, Roche, and Sanofi, is 
      on the Speakers' Bureau for Amgen, Bristol-Myers Squibb, MSD, Novartis, and 
      Roche, received Research Funding from Bristol-Myers Squibb, and Roche, reports 
      travel, accommodations, and expenses from Bristol-Myers Squibb and MSD, and 
      reports other relationship with Avantis Medical Systems.
EDAT- 2021/06/22 06:00
MHDA- 2022/04/15 06:00
CRDT- 2021/06/21 20:14
PHST- 2021/01/07 00:00 [received]
PHST- 2021/05/20 00:00 [revised]
PHST- 2021/06/13 00:00 [accepted]
PHST- 2021/06/22 06:00 [pubmed]
PHST- 2022/04/15 06:00 [medline]
PHST- 2021/06/21 20:14 [entrez]
AID - S0190-9622(21)01991-5 [pii]
AID - 10.1016/j.jaad.2021.06.849 [doi]
PST - ppublish
SO  - J Am Acad Dermatol. 2022 Feb;86(2):345-352. doi: 10.1016/j.jaad.2021.06.849. Epub 
      2021 Jun 18.