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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

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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, Yves | Vey, N.

Edité par CCSD ; Nature Publishing Group -

International audience. 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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