A phase I-II study of plerixafor in combination with fludarabine, idarubicin, cytarabine, and G-CSF (PLERIFLAG regimen) for the treatment of patients with the first early-relapsed or refractory acute myeloid leukemia

Autores de IIS La Fe

• David Martínez Cuadrón

  Autor

• Blanca Boluda Pascual

  Autor

• Paula Martinez Ricart

  Autor

• Rebeca Rodríguez Veiga

  Autor

• Juan Serrano Gandia

  Autor

• Lourdes Cordón Gallego

  Autor

• Amparo Sempere Talens

  Autor

• Beatriz Perez Benavente

  Autor

• Federico Moscardo Garcia

  Autor

• Miguel Ángel Sanz Alonso

  Autor

• Pau Montesinos Fernández

  Autor

Participantes ajenos a IIS La Fe

• Bergua J
• Esteve J
• Vives S
• Vidriales B
• Salamero O
• Jiménez-Ubieto A
• Prieto-Delgado J
• Díaz-Beyá M
• Garrido A
• Pérez-Simón JA
• CETLAM and PETHEMA groups

Grupos

• Hematología y Hemoterapia

Abstract

Clinical outcomes of patients with acute myeloid leukemia (AML) showing the first primary refractory or early-relapsed disease remain very poor. The Programa Espaol de Tratamientos en Hematologia (PETHEMA) group designed a phase I-II trial using FLAG-Ida (fludarabine, idarubicin, cytarabine, and G-CSF) plus high-dose intravenous plerixafor, a molecule inducing mobilization of blasts through the SDF-1 alpha-CXCR4 axis blockade and potentially leading to chemosensitization of the leukemic cells. We aimed to establish a recommended phase 2 dose (RP2D) of plerixafor plus FLAG-Ida, as well as the efficacy and safety of this combination for early-relapsed (first complete remission (CR/CRi) < 12 months) or primary refractory AML. Between 2012 and 2015, 57 patients were enrolled, and 41 received the RP2D (median age 52 years [range, 18-64]). Among these patients, 20 (49%) achieved CR/CRi, and 3 (7%) died during induction. CR/CRi rate was 50% (13/26) among primary refractory and 47% (7/15) among early relapse. Overall, 25 patients (61%) were allografted. Median overall and disease-free survivals were 9.9 and 13 months, respectively. In summary, the combination of plerixafor plus FLAG-Ida resulted in a relatively high CR/CRi rate in adult patients with primary refractory or early relapsed AML, with an acceptable toxicity profile and induction mortality rate, bridging the majority of patients to allogeneic stem cell transplantation. ClinicalTrials.gov Identifier: NCT01435343.

Keywords

• Acute myeloid leukemia; Plerixafor; FLAG-Ida; Resistance; Relapse