PMID- 37549532
OWN - NLM
STAT- MEDLINE
DCOM- 20230829
LR  - 20230830
IS  - 1879-0852 (Electronic)
IS  - 0959-8049 (Linking)
VI  - 191
DP  - 2023 Sep
TI  - Efficacy and safety of crizotinib in ALK-positive systemic anaplastic large-cell 
      lymphoma in children, adolescents, and adult patients: results of the French 
      AcSe-crizotinib trial.
PG  - 112984
LID - S0959-8049(23)00336-2 [pii]
LID - 10.1016/j.ejca.2023.112984 [doi]
AB  - BACKGROUND: The French phase II AcSe-crizotinib trial aimed to evaluate the 
      safety and efficacy of crizotinib in patients with ALK, ROS1, and MET-driven 
      malignancies, including ALK-positive anaplastic large-cell lymphoma (ALK(+) 
      ALCL). METHODS: ALK(+) ALCL patients 12 months or older with measurable disease 
      and no standard care options available received crizotinib twice daily at 
      165 mg/m(2) in children and adolescents and 250 mg in adults. The primary 
      end-point was the response rate at 8 weeks. RESULTS: Twenty-eight patients were 
      enroled between February 2014 and March 2018. Three patients who were not 
      treated were excluded from the analysis. The median age was 19 years. The median 
      previous line of chemotherapy was two. In the 24 patients with an evaluable 
      response, the response rate at 8 weeks was 67% (95% CI: 47-82%). All patients 
      discontinued crizotinib after a median treatment duration of 3.7 months: 
      eight for progression, two for adverse events (AEs) related to prior treatments, 
      and 15 by choice, including six for allogeneic stem-cell transplantation. The 
      median follow-up was 45 months. Nine patients experienced an event: eight 
      relapses (seven after crizotinib discontinuation and one after dose reduction), 
      and one died in complete remission. The median duration of response was 43.3 
      months (95% CI: 8.3-not reached). The 3-year progression-free and overall 
      survival rates were 40% (95% CI: 23-59%) and 63% (95% CI: 43-79%). Grade 3 or 4 
      treatment-related AEs occurred in 32% of patients. CONCLUSION: Crizotinib shows 
      efficacy and an acceptable safety profile in ALK(+) ALCL relapsed/refractory 
      patients. However, a large proportion of patients experience a relapse after 
      crizotinib discontinuation. Future studies will assess if prolonged ALK inhibitor 
      exposure has curative potential without consolidation.
CI  - Copyright (c) 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.
FAU - Brugieres, Laurence
AU  - Brugieres L
AD  - Department of Children and Adolescent Oncology, Gustave Roussy Cancer Campus, 
      Paris-Saclay University, Villejuif, France. Electronic address: 
      laurence.brugieres@gustaveroussy.fr.
FAU - Cozic, Nathalie
AU  - Cozic N
AD  - Service de Biostatistique et d'Epidemiologie, Gustave Roussy, Oncostat U1018 
      INSERM, Labeled Ligue Contre le Cancer, Universite Paris-Saclay, Villejuif, 
      France.
FAU - Houot, Roch
AU  - Houot R
AD  - Department of Hematology, CHU de Rennes, Universite de Rennes, Rennes, France.
FAU - Rigaud, Charlotte
AU  - Rigaud C
AD  - Department of Children and Adolescent Oncology, Gustave Roussy Cancer Campus, 
      Paris-Saclay University, Villejuif, France.
FAU - Sibon, David
AU  - Sibon D
AD  - Lymphoid Malignancies Department, Henri Mondor University Hospital, AP-HP, 
      Creteil, France.
FAU - Arfi-Rouche, Julia
AU  - Arfi-Rouche J
AD  - Department of Radiology, Gustave Roussy Cancer Campus, Paris-Saclay University, 
      Villejuif, France.
FAU - Bories, Pierre
AU  - Bories P
AD  - Institut Universitaire du Cancer - Oncopole, Toulouse, France.
FAU - Cottereau, Anne S
AU  - Cottereau AS
AD  - Department of Nuclear Medicine, Cochin Hospital, AP-HP, University of Paris, 
      Paris, France.
FAU - Delmer, Alain
AU  - Delmer A
AD  - Department of Hematology, University Hospital of Reims and UFR Medecine, Reims, 
      France.
FAU - Ducassou, Stephane
AU  - Ducassou S
AD  - Department of Pediatric Hemato-Oncology, Bordeaux, France.
FAU - Garnier, Nathalie
AU  - Garnier N
AD  - Institut d'Hematologie et d'Oncologie Pediatrique, Hospices Civils de Lyon, Lyon, 
      France.
FAU - Lamant, Laurence
AU  - Lamant L
AD  - Department of Pathology, Institut Universitaire du Cancer de Toulouse Oncopole, 
      Toulouse, France Universite Toulouse III-Paul Sabatier; UMR1037 CRCT, Toulouse, 
      France.
FAU - Leruste, Amaury
AU  - Leruste A
AD  - SIREDO Oncology Center (Care, Innovation and Research for Children and AYA with 
      Cancer), Institut Curie, PSL Research University, Paris, France.
FAU - Millot, Frederic
AU  - Millot F
AD  - Inserm CIC 1402, University Hospital, Poitiers, France.
FAU - Moalla, S
AU  - Moalla S
AD  - Institut Universitaire du Cancer - Oncopole, Toulouse, France.
FAU - Morschhauser, Franck
AU  - Morschhauser F
AD  - ULR 7365 - GRITA - Groupe de Recherche sur les formes Injectables et les 
      Technologies Associees, Univ. Lille, CHU Lille, Lille, France.
FAU - Nolla, Marie
AU  - Nolla M
AD  - Pediatric Hematology-Immunology, CHU Toulouse Purpan, France.
FAU - Pagnier, Anne
AU  - Pagnier A
AD  - Pediatric Immunology Hematology and Oncology, CHU Grenoble Alpes, France.
FAU - Reguerre, Yves
AU  - Reguerre Y
AD  - CHU de Saint Denis de La Reunion Service d'Oncologie et d'Hematologie 
      Pediatrique, Saint Denis, France.
FAU - Renaud, Loic
AU  - Renaud L
AD  - Assistance Publique-Hopitaux de Paris, Hopital Saint-Louis, Hemato-Oncologie, DMU 
      DHI; Universite de Paris, Paris, France.
FAU - Schmitt, Anne
AU  - Schmitt A
AD  - Hematologie, Institut Bergonie, Bordeaux, France.
FAU - Simonin, Mathieu
AU  - Simonin M
AD  - Department of Pediatric Hematology and Oncology, Assistance Publique-Hopitaux de 
      Paris Armand Trousseau Hospital, Sorbonne Universite, Paris, France.
FAU - Verschuur, Arnaud
AU  - Verschuur A
AD  - Department of Pediatric Hematology-Oncology, La Timone University Hospital, APHM, 
      Marseille, France.
FAU - Hoog Labouret, Nathalie
AU  - Hoog Labouret N
AD  - Institut National du Cancer, Boulogne Billancourt, Paris, France.
FAU - Mahier Ait Oukhatar, Celine
AU  - Mahier Ait Oukhatar C
AD  - UNICANCER, Paris, France.
FAU - Vassal, Gilles
AU  - Vassal G
AD  - Department of Children and Adolescent Oncology, Gustave Roussy Cancer Campus, 
      Paris-Saclay University, Villejuif, France.
LA  - eng
SI  - ClinicalTrials.gov/NCT02034981
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230717
PL  - England
TA  - Eur J Cancer
JT  - European journal of cancer (Oxford, England : 1990)
JID - 9005373
RN  - 53AH36668S (Crizotinib)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.1 (Anaplastic Lymphoma Kinase)
RN  - 0 (Proto-Oncogene Proteins)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
RN  - 0 (Protein Kinase Inhibitors)
SB  - IM
MH  - Humans
MH  - Adult
MH  - Child
MH  - Adolescent
MH  - Young Adult
MH  - Crizotinib/therapeutic use
MH  - *Lymphoma, Large-Cell, Anaplastic/drug therapy
MH  - Protein-Tyrosine Kinases/therapeutic use
MH  - Anaplastic Lymphoma Kinase
MH  - Neoplasm Recurrence, Local/drug therapy
MH  - Proto-Oncogene Proteins
MH  - Receptor Protein-Tyrosine Kinases/therapeutic use
MH  - Protein Kinase Inhibitors/adverse effects
MH  - *Lung Neoplasms/drug therapy
OTO - NOTNLM
OT  - ALK inhibitors
OT  - Anaplastic large-cell lymphoma ALK(+)
OT  - Crizotinib
COIS- Declaration of Competing Interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2023/08/08 00:42
MHDA- 2023/08/29 12:42
CRDT- 2023/08/07 18:04
PHST- 2023/04/25 00:00 [received]
PHST- 2023/06/27 00:00 [revised]
PHST- 2023/07/05 00:00 [accepted]
PHST- 2023/08/29 12:42 [medline]
PHST- 2023/08/08 00:42 [pubmed]
PHST- 2023/08/07 18:04 [entrez]
AID - S0959-8049(23)00336-2 [pii]
AID - 10.1016/j.ejca.2023.112984 [doi]
PST - ppublish
SO  - Eur J Cancer. 2023 Sep;191:112984. doi: 10.1016/j.ejca.2023.112984. Epub 2023 Jul 
      17.