Panobinostat as part of induction and maintenance for elderly patients with newly diagnosed acute myeloid leukemia: Phase Ib/II Panobidara study
Ocio EM(1), Herrera P(2), Olave MT(3), Castro N(4), Pérez-Simón JA(5), Brunet S(6), Oriol A(7), Mateo M(8), Sanz MÁ(9), López J(2), Montesinos P(9), Chillón MC(10), Prieto-Conde MI(10), Díez-Campelo M(10), González M(10), Vidriales MB(10), Mateos MV(10), San-Miguel JF(11).
This phase Ib/II trial combined the pan-deacetylase inhibitor panobinostat with chemotherapy followed by panobinostat maintenance in elderly patients with newly diagnosed acute myeloid leukemia. Patients with prior history of myelodisplastic syndrome were excluded.
Thirty-eight evaluable patients (median age, 71 years; range, 65-83) received an induction with idarubicin (8 mg/m2 iv days 1-3) plus cytarabine (100 mg/m2 iv days 1-7) plus panobinostat po at escalating doses (days 8, 10, 12, 15, 17 and 19), that could be repeated in non-responding patients. Patients achieving complete remission received a consolidation cycle with the same schema, followed by panobinostat maintenance (40 mg po 3 days/week) every other week until progression.
Thirty-one patients were treated at the maximum tolerated dose of panobinostat in the combination (10 mg) with good tolerability. The complete remission rate was 64% with a time to relapse of 17.0 months (12.8-21.1). The median overall survival for the whole series was 17 months (5.5-28.4). Moreover, in 4 out of 5 patients with persistent minimal residual disease before maintenance, panobinostat monotherapy reduced its levels, with complete negativization in two of them. Maintenance phase was well tolerated being the most frequent adverse events thrombocytopenia (25% grades 3/4), and gastrointestinal toxicity, asthenia and anorexia mainly grades 1/2. Five patients required dose reduction during this phase, but only one discontinued due to toxicity.
These results suggest that panobinostat is one of the first novel agents with activity in elderly acute myeloid leukemia patients, and warrants its investigation particularly in the context of maintenance therapy. The trial was registered in www.clinicaltrials.gov with number NCT00840346.