In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 78, No. 13_Supplement ( 2018-07-01), p. 3613-3613
Abstract:
Functional profiling is an emerging trend in precision medicine. Manual laboratory methods proved to be effective in predicting the response to drug treatments both in patients stratified according to genetic profiling and in patients without any specific molecular aberration. In this work, we validated the predictive power of an innovative functional profiling platform, based on lab-on-a-chip technology, which allows testing the response of live tumor cells exposed to anticancer drugs in a fully-automated process, requiring only a Ficoll stratification as a manual step. 15 AML patients (Age: 40% & lt;60 years, 46% in the 60-70 years range, 14% & gt;70 years; Gender: 40% Female; ELN Classification: 20% Favorable, 26% Intermediate-I, 33% Intermediate-II, 14% Adverse; AML stage: 53% De novo, 7% Relapse, 40% Refractory; Treatment: 20% FLAI-3, 40% FLAI-5, 26% Decitabine; 7% Cytarabine, 7% 5-azacitidine) were treated at the Policlinico Sant'Orsola in Bologna. At the same time, bone marrow samples were challenged with the same drugs at scaled concentrations in the functional profiling platform developed by CellPly and an output score was extracted from time-lapse fluorescence image analysis of patient tumor cells exposed to the drug or drug combination for 24 hours. Clinical follow up resulted in the following classification: complete hematologic response (CR) was found in 6/15 patients (6/6 with a De Novo disease), while the remaining 9/15 patients (2/9 de novo; 1/9 Relapse; 6/9 Refractory) were classified as stable disease (SD). In-vitro functional profiling of 14 patients provided a correlation with the clinical outcome (p=0.01) irrespective of the stage of the disease. 100% of the patients identified as responders by functional profiling (n = 5), resulted in a CR outcome. 89% of the patients identified as non-responders (n = 9) resulted in an SD outcome. The same patient samples were also investigated for the molecular assessment of the most relevant genes commonly analyzed in AML patients. FLT3-ITD mutation was found in 2/14 patients, both in SD. Negative FLT3 was not correlated to clinical outcome. FLT3-TKD mutation was found in 3/14 patients, 2/3 resulted in CR, 1/3 in SD. TP53 mutation was found in 1/13 patients, classified as SD. Intronic variant rs1625895 was found in 6/13 patients equally distributed in CR and SD. NPM1 mutation was identified in 4/13 patients, 2/4 resulted in CR, 2/4 in SD indicating no direct correlation. IDH2 was found in 1/11 patients (with R172K mutation) with an SD. As a conclusion, functional profiling proved to be highly correlated with clinical outcome irrespective of patient stage and demonstrated a superior predictive power compared to molecular profiling. Citation Format: Laura Rocchi, Andrea Faenza, Viviana Guadagnuolo, Laura Rambelli, Giovanni Marconi, Maria Chiara Fontana, Martina Pazzaglia, Cristina Papayannidis, Giorgia Simonetti, Nicola Pecorari, Luca Giulianelli, Dario Biscarini, Marco Bettelli, Michele Federici, Rita Ruggiano, Giovanni Martinelli, Roberto Guerrieri, Massimo Bocchi. Lab-on-a-chip-based in-vitro functional profiling proves to be effective in predicting therapy outcome in AML patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3613.
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2018-3613
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2018
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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