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A chemogenomic approach to identify personalized therapy for patients with relapse or refractory acute myeloid leukemia: results of a prospective feasibility study

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 che...

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Autores principales: Collignon, A., Hospital, M. A., Montersino, C., Courtier, F., Charbonnier, A., Saillard, C., D’Incan, E., Mohty, B., Guille, A., Adelaïde, J., Carbuccia, N., Garnier, S., Mozziconacci, M. J., Zemmour, C., Pakradouni, J., Restouin, A., Castellano, R., Chaffanet, M., Birnbaum, D., Collette, Y., Vey, N.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7266815/
https://www.ncbi.nlm.nih.gov/pubmed/32488055
http://dx.doi.org/10.1038/s41408-020-0330-5
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author Collignon, A.
Hospital, M. A.
Montersino, C.
Courtier, F.
Charbonnier, A.
Saillard, C.
D’Incan, E.
Mohty, B.
Guille, A.
Adelaïde, J.
Carbuccia, N.
Garnier, S.
Mozziconacci, M. J.
Zemmour, C.
Pakradouni, J.
Restouin, A.
Castellano, R.
Chaffanet, M.
Birnbaum, D.
Collette, Y.
Vey, N.
author_facet Collignon, A.
Hospital, M. A.
Montersino, C.
Courtier, F.
Charbonnier, A.
Saillard, C.
D’Incan, E.
Mohty, B.
Guille, A.
Adelaïde, J.
Carbuccia, N.
Garnier, S.
Mozziconacci, M. J.
Zemmour, C.
Pakradouni, J.
Restouin, A.
Castellano, R.
Chaffanet, M.
Birnbaum, D.
Collette, Y.
Vey, N.
author_sort Collignon, A.
collection PubMed
description 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.
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spelling pubmed-72668152020-06-16 A chemogenomic approach to identify personalized therapy for patients with relapse or refractory acute myeloid leukemia: results of a prospective feasibility study Collignon, A. Hospital, M. A. Montersino, C. Courtier, F. Charbonnier, A. Saillard, C. D’Incan, E. Mohty, B. Guille, A. Adelaïde, J. Carbuccia, N. Garnier, S. Mozziconacci, M. J. Zemmour, C. Pakradouni, J. Restouin, A. Castellano, R. Chaffanet, M. Birnbaum, D. Collette, Y. Vey, N. Blood Cancer J Article 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. Nature Publishing Group UK 2020-06-03 /pmc/articles/PMC7266815/ /pubmed/32488055 http://dx.doi.org/10.1038/s41408-020-0330-5 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Collignon, A.
Hospital, M. A.
Montersino, C.
Courtier, F.
Charbonnier, A.
Saillard, C.
D’Incan, E.
Mohty, B.
Guille, A.
Adelaïde, J.
Carbuccia, N.
Garnier, S.
Mozziconacci, M. J.
Zemmour, C.
Pakradouni, J.
Restouin, A.
Castellano, R.
Chaffanet, M.
Birnbaum, D.
Collette, Y.
Vey, N.
A chemogenomic approach to identify personalized therapy for patients with relapse or refractory acute myeloid leukemia: results of a prospective feasibility study
title A chemogenomic approach to identify personalized therapy for patients with relapse or refractory acute myeloid leukemia: results of a prospective feasibility study
title_full A chemogenomic approach to identify personalized therapy for patients with relapse or refractory acute myeloid leukemia: results of a prospective feasibility study
title_fullStr A chemogenomic approach to identify personalized therapy for patients with relapse or refractory acute myeloid leukemia: results of a prospective feasibility study
title_full_unstemmed A chemogenomic approach to identify personalized therapy for patients with relapse or refractory acute myeloid leukemia: results of a prospective feasibility study
title_short A chemogenomic approach to identify personalized therapy for patients with relapse or refractory acute myeloid leukemia: results of a prospective feasibility study
title_sort chemogenomic approach to identify personalized therapy for patients with relapse or refractory acute myeloid leukemia: results of a prospective feasibility study
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7266815/
https://www.ncbi.nlm.nih.gov/pubmed/32488055
http://dx.doi.org/10.1038/s41408-020-0330-5
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