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  3. Ponatinib, Chemotherapy, and Transplant in Adults with Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia.

Ponatinib, Chemotherapy, and Transplant in Adults with Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia.

Fecha de publicación: Fecha Ahead of Print:

Autores de IIS La Fe

Participantes ajenos a IIS La Fe

  • Ribera, Josep-Maria
  • Garcia-Calduch, Olga
  • Ribera, Jordi
  • Cano-Ferri, Isabel
  • Martinez, Pilar
  • Esteve, Jordi
  • Esteban, Daniel
  • Garcia-Fortes, Maria
  • Alonso, Natalia
  • Gonzalez-Campos, Jose
  • Bermudez, Arancha
  • Torrent, Anna
  • Genesca, Eulalia
  • Mercadal, Santiago
  • Martinez-Lopez, Joaquin
  • Garcia-Sanz, Ramon

Grupos

Abstract

Promising results have been shown combining ponatinib and chemotherapy in adults with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL). The PONALFIL trial combined ponatinib (30 mg/day) with standard induction and consolidation chemotherapy followed by allogeneic hematopoietic stem cell transplant (alloHSCT) in newly diagnosed Ph+ALL patients aged 18-60 years. Ponatinib was only given pre-emptively after alloHSCT. Primary endpoints were hematologic and molecular response before alloHSCT and event-free survival (EFS), including molecular relapse as event. Thirty patients (median age 49 [19-59] years) entered the trial. All showed hematologic response, and alloHSCT was performed in 26 patients (20 in complete molecular response and 6 in major molecular response). Only one patient died by graft-versus-host disease and 5 patients showed molecular relapse after alloHSCT. No tyrosine kinase inhibitor (TKI) was given after HSCT in 18/26 patients. Twenty-nine patients are alive (median follow-up 2.1 years, range 0.2-4.0), with 3-year EFS and overall survival (OS) of 70% (95% CI, 51%-89%) and 96% (89%-100%). Comparison of the PONALFIL and the ALLPh08 trials (same schedule using imatinib as TKI ) by propensity score showed significant improvement in OS for patients in PONALFIL (3-year OS 96% vs. 53%, p=0.002). The most frequent grade 3-4 adverse events were hematologic (42%), infections (17%) and hepatic (22%), with only one vascular occlusive event. The combination of chemotherapy with ponatinib followed by alloHSCT is well tolerated, with encouraging EFS in adults with newly diagnosed Ph+ALL. Cross-trial comparison suggests improvement versus imatinib. (Clinicaltrials.gov NCT02776605).

© 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.

Datos de la publicación

ISSN/ISSNe:
2473-9529, 2473-9537

Blood Advances  ELSEVIER

Tipo:
Article
Páginas:
5395-5402
PubMed:
35675590
Factor de Impacto:
2,795 SCImago ℠
Cuartil:
Q1 SCImago ℠

Citas Recibidas en Web of Science: 53

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Keywords

  • HYPER-CVAD; PROPENSITY SCORE; 1ST-LINE THERAPY; SINGLE-CENTER; IMATINIB; DASATINIB; COMBINATION

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