Details

Autor(en) / Beteiligte

• Ribera, Josep-Maria
• García-Calduch, Olga
• Ribera, Jordi
• Montesinos, Pau
• Cano-Ferri, Isabel
• Martínez, Pilar
• Esteve, Jordi
• Esteban, Daniel
• García-Fortes, María
• Alonso, Natalia
• González-Campos, José
• Bermúdez, Arancha
• Torrent, Anna
• Genescà, Eulàlia
• Mercadal, Santiago
• Martínez-Lopez, Joaquín
• García-Sanz, Ramón

Titel

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

Ist Teil von

• Blood advances, 2022-09, Vol.6 (18), p.5395-5402

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2022

Link zum Volltext

Quelle

Elektronische Zeitschriftenbibliothek (Open access)

Beschreibungen/Notizen

• 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).