Treatment of higher risk myelodysplastic syndrome patients unresponsive to hypomethylating agents with ON 01910.Na

Abstract

In a Phase I/II clinical trial, 13 higher risk red blood cell-dependent myelodysplastic syndrome (MDS) patients unresponsive to hypomethylating therapy were treated with the multikinase inhibitor ON 01910.Na. Responses occurred in all morphologic, prognostic risk and cytogenetic subgroups, including four patients with marrow complete responses among eight with stable disease, associated with good drug tolerance. In a subset of patients, a novel nanoscale immunoassay showed substantially decreased AKT2 phosphorylation in CD34+ marrow cells from patients responding to therapy but not those who progressed on therapy. These data demonstrate encouraging efficacy and drug tolerance with ON 01910.Na treatment of higher risk MDS patients.

Conflict of interest statement

Conflict of interests: Peter Greenberg received research funding for this study from Onconova Therapeutics Inc. Francois Wilhelm is Chief Medical Officer and Senior Vice President at Onconova Therapeutics Inc. Dean Felsher is on the Scientific Advisory Board for Cell Biosciences. The other co-authors declare no competing financial interests.

Copyright © 2011 Elsevier Ltd. All rights reserved.

Figures

Figure 1

Overall survival of patients treated with ON 01910.Na from the onset of start of study drug therapy (Kaplan-Meier curve).

Figure 2

Treatment effects of ON 01910.Na on AKT2 phosphorylation using nanoimmunoassay (NIA) analysis: Decreased phosphorylation in CD34+ marrow cells in (a) a responding MDS patient (#101) with stable disease, (b) in a responding patient (#104) with marrow complete response, and (c) in a nonresponder (#111) whose disease progressed on treatment.