In:
Blood, American Society of Hematology, Vol. 116, No. 21 ( 2010-11-19), p. 4359-4359
Abstract:
Abstract 4359 We conducted a phase I-II study aiming to assess efficacy and toxicity of tipifarnib-bortezomib treatment in elderly AML patients. RASGRP1/APTX genetic ratio, which is associated with treatment response in patients treated with tipifarnib alone, was tested. Eighty patients were enrolled with secondary-AML: 14 had high risk cytogenetics; 42 were previously untreated. Seventy-five patients were treated. Nine patients achieved complete remission (CR), 1 patient obtained a partial response (PR) and in 2 cases an hematological improvement (HI) was documented for an overall response rate (ORR) of 19%. Median time to response was 112 days, corresponding to 4 cycles (range 2–14). Marrow response (CR+PR) was significantly associated with overall survival (OS) (p 〈 0.0001). RASGRP1/APTX was evaluated before treatment initiation on bone marrow (BM), peripheral blood (PB) or both. The median RASGRP/APTX value on BM was 15.3 (15-19.8) in responder patients and 2.2 (0.5-25.9) in non responders, respectively (p=0.00006). Its median value on PB was 31.6 (19.3-35.5) in responders and 6.4 (0.5-27.1) in non responders, respectively (p=0.00001). Interestingly, no marrow responses were recorded in patients with marrow RASGRP1/APTX ratio 〈 8, while the response rate was 43% [how many were CR?] in patients with RASGRP1/APTX 〉 8 (p 〈 0.0001). Finally, RASGRP1/APTX levels significantly correlated with OS (p=0.001) with a median OS of 490 days and 162 days in patients with RASGRP1/APTX 〉 8 and 〈 8 respectively. We conclude that the clinical efficacy of the combination of tipifarnib and bortezomib was evident. We confirmed that the RASGPR1/APTX BM or PB level is an effective predictor of response and survival and our now studying the response of such patients to tipifarnib, alone. Supported by: European LeukemiaNet, AIL, AIRC, Fondazione Del Monte di Bologna e Ravenna, FIRB 2006, PRIN 2008, Ateneo RFO grants, Project of integrated program (PIO), Programma di Ricerca Regione – Università 2007 – 2009. Disclosures: Martinelli: Novartis: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Pfizer: Consultancy. Baccarani:Novartis: Consultancy, Honoraria; BMS: Consultancy, Honoraria.
Type of Medium:
Online Resource
ISSN:
0006-4971
,
1528-0020
DOI:
10.1182/blood.V116.21.4359.4359
Language:
English
Publisher:
American Society of Hematology
Publication Date:
2010
detail.hit.zdb_id:
1468538-3
detail.hit.zdb_id:
80069-7
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