RT Journal Article
T1 Ponatinib, chemotherapy, and transplant in adults with Philadelphia chromosome-positive acute lymphoblastic leukemia.
A1 Ribera, Josep-Maria
A1 Garcia-Calduch, Olga
A1 Ribera, Jordi
A1 Montesinos, Pau
A1 Cano-Ferri, Isabel
A1 Martinez, Pilar
A1 Esteve, Jordi
A1 Esteban, Daniel
A1 Garcia-Fortes, Maria
A1 Alonso, Natalia
A1 Gonzalez-Campos, Jose
A1 Bermudez, Arancha
A1 Torrent, Anna
A1 Genesca, Eulalia
A1 Mercadal, Santiago
A1 Martinez-Lopez, Joaquin
A1 Garcia-Sanz, Ramon
K1 Imatinib Mesylate
K1 Antineoplastic Combined Chemotherapy Protocols
K1 Imidazoles
K1 Precursor Cell Lymphoblastic Leukemia-Lymphoma
K1 Young Adult
AB Promising results have been shown with the combination of ponatinib and chemotherapy in adults with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). The PONALFIL (Ponatinib With Chemotherapy for Young Adults Ph Positive Acute Lymphoblastic Leukemia) trial combined ponatinib (30 mg/d) with standard induction and consolidation chemotherapy followed by allogeneic hematopoietic stem cell transplant (alloHSCT) in newly diagnosed Ph+ ALL patients aged 18 to 60 years. Ponatinib was only given pre-emptively after alloHSCT. Primary end points were hematologic and molecular response before alloHSCT and event-free survival (EFS), including molecular relapse as event. Thirty patients (median age, 49 years; range, 19-59 years) entered the trial. All exhibited hematologic response, and alloHSCT was performed in 26 patients (20 in complete molecular response and 6 in major molecular response). Only 1 patient died (of graft-versus-host disease), and 5 patients exhibited molecular relapse after alloHSCT. No tyrosine kinase inhibitor was given after HSCT in 18 of 26 patients. Twenty-nine patients are alive (median follow-up, 2.1 years; range, 0.2-4.0 years), with 3-year EFS and overall survival (OS) of 70% (95% confidence interval, 51-89) and 96% (95% confidence interval, 89-100), respectively. Comparison of the PONALFIL and the ALLPh08 (Chemotherapy and Imatinib in Young Adults With Acute Lymphoblastic Leukemia Ph [BCR-ABL] Positive; same schedule, using imatinib as the tyrosine kinase inhibitor) trials by propensity score showed significant improvement in OS for patients in PONALFIL (3-year OS, 96% vs 53%; P = .002). The most frequent grade 3 to 4 adverse events were hematologic (42%), infectious (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 vs imatinib (clinicaltrials.gov identifier #NCT02776605).
PB American Society of Hematology
YR 2022
FD 2022-09-22
LK http://hdl.handle.net/10668/20253
UL http://hdl.handle.net/10668/20253
LA en
NO Ribera JM, García-Calduch O, Ribera J, Montesinos P, Cano-Ferri I, Martínez P, et al. Ponatinib, chemotherapy, and transplant in adults with Philadelphia chromosome-positive acute lymphoblastic leukemia. Blood Adv. 2022 Sep 27;6(18):5395-5402.
NO The authors thank Incyte for providing ponatinib to all study patients free of cost, to CABYC for helping in the conduction of the trial, and to the following institutions for their contribution to the study: ICO-Hospital Germans Trias i Pujol, Josep Carreras Leukemia Research Institute (IJC) (J.-M.R., O.G.-C., J.R., A.T., and E.G.); Hospital Universitari i Politècnic La Fe (P. Montesinos, I.C.-F.); Hospital Doce De Octubre (P. Martínez, J.M.-L.); Hospital Clínic (J.E. and D.E.); Hospital Universitario Virgen De La Victoria (M.G.-F.); Complejo Hospitalario Universitario Santiago de Compostela (N.A.); Hospital Universitario Virgen del Rocío (J.G.-C.); Hospital Universitario Marqués de Valdecilla (A.B.); ICO-Hospital Duran i Reynals (S.M.); and Hospital Universitario de Salamanca (HUS/IBSAL), CIBERONC and Center for Cancer Research-IBMCC (USAL-CSIC) (R.G.-S.).The PETHEMA Foundation, a nonprofit organization, was the sponsor of the trial, and the PETHEMA Data Center elaborated the database, and organized training meetings in which principal investigators and collaborative investigators participated. This project was supported in part by the ISCIII (PI14/01971 and PI19/01828), cofunded by ERDF/ESF, “A way to make Europe”/“Investing in your future,” CERCA/Generalitat de Catalunya SGR 2017 288 (GRC)/“La Caixa.” This project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement no. 116026. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation and the European Federation of Pharmaceutical Industries and Associations.
DS RISalud
RD Jul 3, 2025