A chemogenomic approach to identify personalized therapy for patients with relapse or refractory acute myeloid leukemia: results of a prospective feasibility study.
Adult
Aged
Aged, 80 and over
Antineoplastic Agents
/ pharmacology
Feasibility Studies
Female
Genomics
/ methods
High-Throughput Nucleotide Sequencing
Humans
Leukemia, Myeloid, Acute
/ drug therapy
Male
Middle Aged
Molecular Targeted Therapy
/ methods
Mutation
/ drug effects
Neoplasm Recurrence, Local
/ drug therapy
Precision Medicine
/ methods
Prospective Studies
Young Adult
Journal
Blood cancer journal
ISSN: 2044-5385
Titre abrégé: Blood Cancer J
Pays: United States
ID NLM: 101568469
Informations de publication
Date de publication:
03 06 2020
03 06 2020
Historique:
received:
26
12
2019
accepted:
23
04
2020
revised:
06
04
2020
entrez:
4
6
2020
pubmed:
4
6
2020
medline:
11
5
2021
Statut:
epublish
Résumé
Targeted next-generation sequencing (tNGS) and ex vivo drug sensitivity/resistance profiling (DSRP) have laid foundations defining the functional genomic landscape of acute myeloid leukemia (AML) and premises of personalized medicine to guide treatment options for patients with aggressive and/or chemorefractory hematological malignancies. Here, we have assessed the feasibility of a tailored treatment strategy (TTS) guided by systematic parallel ex vivo DSRP and tNGS for patients with relapsed/refractory AML (number NCT02619071). A TTS issued by an institutional personalized committee could be achieved for 47/55 included patients (85%), 5 based on tNGS only, 6 on DSRP only, while 36 could be proposed on the basis of both, yielding more options and a better rationale. The TSS was available in <21 days for 28 patients (58.3%). On average, 3 to 4 potentially active drugs were selected per patient with only five patient samples being resistant to the entire drug panel. Seventeen patients received a TTS-guided treatment, resulting in four complete remissions, one partial remission, and five decreased peripheral blast counts. Our results show that chemogenomic combining tNGS with DSRP to determine a TTS is a promising approach to propose patient-specific treatment options within 21 days.
Identifiants
pubmed: 32488055
doi: 10.1038/s41408-020-0330-5
pii: 10.1038/s41408-020-0330-5
pmc: PMC7266815
doi:
Substances chimiques
Antineoplastic Agents
0
Banques de données
ClinicalTrials.gov
['NCT02619071']
Types de publication
Clinical Trial
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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