Personalized Medicine Test of Multi-Drug Protocols Ex Vivo for Hematological Malignancies

• Published in: Blood 2009-11, Vol.114 (22), p.2655-2655
• Main Authors: Bennett, Teresa A, Sapia, Sandra, Primo, Daniel, Suarez, Lilia, Lago, Santiago, Matoses, Maria, Espinosa, Ana, Tudela, Consuelo, Arroyo, Elena, Gorrochategui, Julian, Jackson, William C, Okun, Alex, Lopez, Horacio Hector, Gornemann, Isolde, Melcon, Soledad Gallego, de Heredia, Cristina Diaz, Dapena, Jose Luis, Roma, Josep M, Delgado, Regina Garcia, Queipodellano, Mari Paz, Bailen, Alicia, Barrios, Manuel, Diez, Eva, Del Castillo, Santiago, Heiniger, Ana Isabel, de Toledo, Jose Sanchez, Ramirez, Manuel, Ortiz, Macarena, Gonzáalez, Marcos, San-Miguel, Jesús F., Ocio, Enrique M, Bosanquet, Andrew G., Orfao, Alberto, Ballesteros, Joan
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V114.22.2655.2655

Abstract 2655 Poster Board II-631 The predictive power of measuring the effect of anticancer treatments on whole living tumor cells freshly removed from cancer patients, called Individualized Tumor Response Testing (ITRT), has been recently further validated in a clinical trial, the UK's LRF CLL4 trial (Bosanquet ASH 2007). It predicts resistance better than sensitivity. We present a novel approach to ITRT based on measuring drug induced apoptosis of tumor cells in whole blood ex vivo (in vitro using freshly extracted samples). It uses a novel automated flow cytometry platform (ExviTech) capable of evaluating hundreds of drugs and drug combinations used in current treatment protocols, and can address the significant scaling of potential future protocols induced by a number of new drug approvals in each indication. We evaluated 47 samples of peripheral blood or bone marrow from patients diagnosed with hematological malignancies: 20 chronic Lymphocytic Leukemia (CLL), 14 Acute Lymphoblastic Leukemia (ALL), 7 Multiple Myeloma (MM), and 6 Acute Myeloblastic Leukemia (AML). After informed consent, samples, collected into heparin, were processed the same or the next day. Whole blood was diluted and incubated with drugs for 24 and 48 hours. Whole blood was used to retain erythrocytes and serum proteins enabling more clinically relevant physiological conditions. Three types of drugs were tested: 1) Approved drugs for each indication, including all possible pair wise combinations, and combinations administered within current and experimental protocols as advised by the PETHEMA groups in Spain. 2) Concomitant medicines (Con-Meds), including alternative drugs within the same class of antacids, antiemetics, etc… to test whether they may also induce apoptosis 3) Drugs in clinical trials, preferentially Phase III drugs, alone and in combination with approved drugs, which may form the basis of future treatment protocols. Drugs were plated at a final concentration equivalent to their reported plasma Cmax concentration. Synergistic drug combinations were identified as one drug potentiating the effect of the other. The efficacy of each drug and combination tested was categorized as highly resistant, intermediate or highly sensitive. Highly resistant drug results were contraindicated. Among the highly sensitive treatments ex vivo, often those that effectively killed all malignant cells, we selected those whose drugs were significantly less toxic as treatment guidelines, high