RASGRP1:APTX Gene Expression Ratio Enriches for Responders to the Combination of Tipifarnib and Etoposide in Elderly Newly Diagnosed AML.

Abstract 4154

A 2-gene ratio (RASGRP1:APTX) has previously been shown to predict response to the single agent farnesyltransferase inhibitor, tipifarnib, in patients with both newly diagnosed or relapsed and refractory acute myeloid leukemia (AML) (Raponi et al. Blood 2008, 111:2589). Here we investigated the utility of the 2-gene ratio to predict response to the combination of tipifarnib and etoposide (VP16) in a phase 1 study (Karp et al. Blood 2009, 113:4841) and continuing phase 2 study of elderly patients with newly diagnosed AML. A Taqman quantitative RT-PCR assay was performed on leukemic blasts from a total of 81 patients who were evaluable for response. A receiver operator characteristic analysis indicated that the predictive value of the 2-gene ratio was 76% for predicting overall response (CR+PR) in the Phase 1 study (51 patients). When using an optimized cutoff the overall response rate doubled from 25% to 50% with a negative predictive value of 88% (p = 0.008). These data indicate that the RASGRP1:APTX gene ratio has utility in predicting response to the combination of tipifarnib and etoposide in elderly newly diagnosed AML. This assay could find broader utility in enriching for responders to tipifarnib combination therapy.