Panobinostat as part of induction and maintenance for elderly patients with newly diagnosed acute myeloid leukemia: phase Ib/II panobidara study

Fecha de publicación: 01/10/2015

Autores de IIS La Fe

Miguel Ángel Sanz Alonso

Autor
Pau Montesinos Fernández

Autor

Participantes ajenos a IIS La Fe

Ocio EM
Herrera P
Olave MT
Castro N
Pérez-Simón JA
Brunet S
Oriol A
Mateo M
López J
Chillón MC
Prieto-Conde MI
Díez-Campelo M
González M
Vidriales MB
Mateos MV
San Miguel JF
PETHEMA Group

Grupos

Hematología y Hemoterapia

Investigador Principal

Javier De La Rubia Comos

Abstract

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 myelodysplastic syndrome were excluded and 38 evaluable patients were included in the study (median age: 71 years; range: 65-83). Study patients received an induction with idarubicin (8 mg/m(2) 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. Complete remission rate was 64% with a time to relapse of 17.0 months (12.8-21.1). Median overall survival for the whole series was 17 months (5.5-28.4). Moreover, in 4 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. The most frequent adverse events were 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 therapy due to toxicity. These results suggest that panobinostat is one of the first novel agents with activity in elderly acute myeloid leukemia patients, and suggest further investigation is warranted, particularly in the context of maintenance therapy.

Datos de la publicación

ISSN/ISSNe:: 0390-6078, 1592-8721
Tipo:: Article
Páginas:: 1294-1300
DOI:: 10.3324/haematol.2015.129577
Factor de Impacto:: 2,959 SCImago ℠
Cuartil:: Q1 SCImago ℠

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Keywords

MINIMAL RESIDUAL DISEASE; MYELODYSPLASTIC SYNDROMES; POSTREMISSION THERAPY; CELL TRANSPLANTATION; POOR-PROGNOSIS; OLDER-ADULTS; OPEN-LABEL; II TRIAL; VORINOSTAT; OUTCOMES

Campos de estudio

Proyectos asociados

RED DE INVESTIGACION COOPERATIVA DE CANCER

RD06/0020/0031 . INSTITUTO DE SALUD CARLOS III; FUNDACIÓN PARA LA INVESTIGACIÓN DEL HOSPITAL UNIVERSITARIO LA FE DE LA COMUNIDAD VALENCIANA . 2006

PROYECTO CAIBER

CAI08/01/0061 . INSTITUTO DE SALUD CARLOS III; FUNDACIÓN PARA LA INVESTIGACIÓN DEL HOSPITAL UNIVERSITARIO LA FE DE LA COMUNIDAD VALENCIANA . 2009

CREACION Y MEJORA DE INFRAESTRUCTURAS EN MEDICINA REGENERATIVA

Investigador Principal: FUNDACIÓN PARA LA INVESTIGACIÓN DEL HOSPITAL UNIVERSITARIO LA FE DE LA COMUNIDAD VALENCIANA

PLE2009-0141 ACI-PLAN E . MINISTERIO DE CIENCIA E INNOVACION; FUNDACIÓN PARA LA INVESTIGACIÓN DEL HOSPITAL UNIVERSITARIO LA FE DE LA COMUNIDAD VALENCIANA . 2009