Comparison of non-myeloablative lymphodepleting preconditioning regimens in patients undergoing adoptive T cell therapy.
Adult
Clinical Trials, Phase II as Topic
Cyclophosphamide
/ adverse effects
Cytokines
/ blood
Female
Humans
Immunotherapy, Adoptive
/ adverse effects
Length of Stay
Lymphocyte Depletion
/ adverse effects
Male
Melanoma
/ immunology
Middle Aged
Myeloablative Agonists
/ adverse effects
Receptors, Chimeric Antigen
/ genetics
Recovery of Function
Skin Neoplasms
/ immunology
T-Lymphocytes
/ immunology
Time Factors
Transplantation Conditioning
/ adverse effects
Treatment Outcome
Vidarabine
/ analogs & derivatives
Whole-Body Irradiation
/ adverse effects
adoptive
chimeric antigen
clinical trials
immunotherapy
lymphocytes
phase II as topic
receptors
tumor-infiltrating
Journal
Journal for immunotherapy of cancer
ISSN: 2051-1426
Titre abrégé: J Immunother Cancer
Pays: England
ID NLM: 101620585
Informations de publication
Date de publication:
05 2021
05 2021
Historique:
accepted:
19
03
2021
entrez:
15
5
2021
pubmed:
16
5
2021
medline:
6
1
2022
Statut:
ppublish
Résumé
Adoptive cell therapy with T cells genetically engineered to express a chimeric antigen receptor (CAR-T) or tumor-infiltrating T lymphocytes (TIL) demonstrates impressive clinical results in patients with cancer. Lymphodepleting preconditioning prior to cell infusion is an integral part of all adoptive T cell therapies. However, to date, there is no standardization and no data comparing different non-myeloablative (NMA) regimens. In this study, we compared NMA therapies with different doses of cyclophosphamide or total body irradiation (TBI) in combination with fludarabine and evaluated bone marrow suppression and recovery, cytokine serum levels, clinical response and adverse events. We demonstrate that a cumulative dose of 120 mg/kg cyclophosphamide and 125 mg/m Bone marrow depletion and recovery were equally affected by 120Cy/125Flu and 60Cy/125Flu preconditioning; however, toxicity and consequently duration of hospitalization were significantly lower in the 60Cy/125Flu cohort. Patients in the 30Cy/75Flu and TBI/75Flu groups rarely developed NMA-induced adverse events; however, both regimens were not efficient in achieving deep bone marrow suppression. Among the regimens, 60Cy/125Flu preconditioning seems to achieve maximum effect with minimum toxicity.
Sections du résumé
BACKGROUND
Adoptive cell therapy with T cells genetically engineered to express a chimeric antigen receptor (CAR-T) or tumor-infiltrating T lymphocytes (TIL) demonstrates impressive clinical results in patients with cancer. Lymphodepleting preconditioning prior to cell infusion is an integral part of all adoptive T cell therapies. However, to date, there is no standardization and no data comparing different non-myeloablative (NMA) regimens.
METHODS
In this study, we compared NMA therapies with different doses of cyclophosphamide or total body irradiation (TBI) in combination with fludarabine and evaluated bone marrow suppression and recovery, cytokine serum levels, clinical response and adverse events.
RESULTS
We demonstrate that a cumulative dose of 120 mg/kg cyclophosphamide and 125 mg/m
CONCLUSIONS
Bone marrow depletion and recovery were equally affected by 120Cy/125Flu and 60Cy/125Flu preconditioning; however, toxicity and consequently duration of hospitalization were significantly lower in the 60Cy/125Flu cohort. Patients in the 30Cy/75Flu and TBI/75Flu groups rarely developed NMA-induced adverse events; however, both regimens were not efficient in achieving deep bone marrow suppression. Among the regimens, 60Cy/125Flu preconditioning seems to achieve maximum effect with minimum toxicity.
Identifiants
pubmed: 33990415
pii: jitc-2020-001743
doi: 10.1136/jitc-2020-001743
pmc: PMC8127974
pii:
doi:
Substances chimiques
Cytokines
0
Myeloablative Agonists
0
Receptors, Chimeric Antigen
0
Cyclophosphamide
8N3DW7272P
Vidarabine
FA2DM6879K
fludarabine
P2K93U8740
Banques de données
ClinicalTrials.gov
['NCT00287131', 'NCT03166397', 'NCT02772198']
Types de publication
Comparative Study
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
Déclaration de conflit d'intérêts
Competing interests: No, there are no competing interests.
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