Randomized, phase 2 trial comparing low-dose cytarabine with or without volasertib in AML patients not suitable for intensive induction therapy

Hartmut Döhner, Michael Lübbert, Walter Fiedler, Loic Fouillard, Alf Haaland, Joseph M. Brandwein, Stephane Lepretre, Oumedaly Reman, Pascal Turlure, Oliver G. Ottmann, Carsten Müller-Tidow, Alwin Krämer, Emmanuel Raffoux, Konstanze Döhner, Richard F. Schlenk, Florian Voss, Tillmann Taube, Holger Fritsch and Johan Maertens

Key points

  • Volasertib plus low-dose cytarabine increased the response rate and improved survival in AML patients ineligible for intensive treatment.

  • Volasertib plus low-dose cytarabine resulted in responses across all AML genetic subgroups and had a clinically manageable safety profile.


Treatment outcomes for older patients with acute myeloid leukemia (AML) have remained dismal. This randomized, phase 2 trial in AML patients not considered suitable for intensive induction therapy compared low-dose cytarabine (LDAC) with or without volasertib, a highly potent and selective inhibitor of polo-like kinases. Eighty-seven patients (median age 75 years) received LDAC 20 mg b.i.d. subcutaneously days 1-10 or LDAC + volasertib 350 mg intravenously days 1 + 15, every 4 weeks. Response rate (complete remission [CR] and CR with incomplete blood count recovery [CRi]) was higher for LDAC + volasertib versus LDAC (31.0% vs 13.3%; odds ratio, 2.91; P=.052). Responses in the LDAC + volasertib arm were observed across all genetic groups, including 5 of 14 patients with adverse cytogenetics. Median event-free survival was significantly prolonged by LDAC + volasertib compared with LDAC (5.6 vs 2.3 months; hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.35-0.92; P=.021); median overall survival was 8.0 versus 5.2 months, respectively (HR, 0.63; 95% CI, 0.40-1.00; P=.047). LDAC + volasertib led to an increased frequency of adverse events that was most pronounced for neutropenic fever/infections and gastrointestinal events; there was no increase in the death rate at days 60 + 90. This study was registered at, identifier: NCT00804856.

  • Submitted March 7, 2014.
  • Accepted June 18, 2014.