CURRENT DOSE RECOMMENDATIONS FOR PONATINIB IN CHRONIC MYELOID LEUKEMIA PATIENTS CAN DIMINISH ADVERSE EVENTS WHILE MAINTAINING EFFICACY
Author(s): ,
Valentin Garcia-Gutierrez
Affiliations:
Hematology,Hospital Universitario Ramon y Cajal,Madrid,Spain
,
Juan Carlos Hernandez-Boluda
Affiliations:
Hematology,Hospital Clinico Universitario de Valencia,Valencia,Spain
,
Beatriz Moiraghi
Affiliations:
Hospital JM Ramos Mejia,Buenos Aires,Argentina
,
Elżbieta Szczepanek Tomasz Sacha
Affiliations:
Hematology, Jagiellonian University Hospital,Krakow,Poland
,
Carolina Pavlovsky
Affiliations:
Hematology,Fundaleu,Buenos Aires,Argentina
,
Olga Grzybowska-Izydorczyk
Affiliations:
Hematology,Medical University in Łódź,Łódź,Poland
,
Juan Correa
Affiliations:
Hospital Clinic,Barcelona,Spain
,
Raul Perez Lopez
Affiliations:
Hematology,Hospital Clinico Universitario Virgen de la Arrixaca,Murcia,Spain
,
Elżbieta Patkowska Joanna Góra-Tybor
Affiliations:
Hematology,Institute of Hematology and Transfusion Medicine,Warsaw,Poland
,
Andres Novo Garcia
Affiliations:
Hematology,Hospital de Son Espases,Mallorca,Spain
,
Santiago Osorio Prendes
Affiliations:
Hospital Gregorio Marañon,Madrid,Spain
,
Rolando Vallansot
Affiliations:
Hospital Universitari Joan XXIII,Tarragona,Spain
,
Angel Ramirez Payer
Affiliations:
Hospital Universitario central de Asturias,Oviedo,Spain
,
Ewa Wasilewska
Affiliations:
Hematology,Medical University of Białystok,Białystok,Poland
,
Miguel Piris Villaespesa
Affiliations:
Hematology,Hospital Universitario Ramon y Cajal,Madrid,Spain
,
Concepcion Boque Genovard
Affiliations:
Hematology,ICO,Barcelona,Spain
,
Manuel Perez Encinas
Affiliations:
Hospital Clínico Universitario de Santiago de Compostela,Santiago de Compostela,Spain
,
Antonio Jimenez Velasco
Affiliations:
Hospital Regional Universitario de Málaga,Málaga,Spain
,
Fermin Sanchez-Guijo
Affiliations:
Hospital Universitario de Salamanca,Salamanca,Spain
,
Mario Andres Romo Collada
Affiliations:
Hospital Meixoeiro,Vigo,Spain
,
Maria Teresa Gomez Casares
Affiliations:
Hospital Universitario de Gran Canaria Dr. Negrín,Gran Canaria,Spain
,
Guillermo Orti Pascual
Affiliations:
Hospital Universitario Vall d´Hebron,Barcelona,Spain
,
Maria Soledad Duran
Affiliations:
Hematology,Hospital Universitario Médico Quirúrgico,Jaen,Spain
,
Angeles Portero
Affiliations:
Hematology,Hospital Universitario Virgen Macarena,Sevilla,Spain
,
Maria Isabel Mata
Affiliations:
Hospital Costa del Sol,Marbella,Spain
,
Maria Soledad Noya
Affiliations:
Hematology,Complejo Hospitalario Universitario A Coruña,A Coruña,Spain
,
Gonzalo Caballero
Affiliations:
Hematology,Hospital Universitario Miguel Servet de Zaragoza,Zaragoza,Spain
,
Nuria Garcia
Affiliations:
Hospital Virgen de la Salud,Toledo,Spain
,
Diego Robles de Castro
Affiliations:
Hospital Universitario de Álava,Vitoria-Gasteiz,Spain
,
Maria Jose Ramirez
Affiliations:
Hospital del SAS de Jerez de la Fra,Jerez de la Frontera,Spain
,
Alicia Senin Magan
Affiliations:
Hematology,Hospital del Mar,Barcelona,Spain
,
Sunil Lakhwani
Affiliations:
Hospital Universitario de Canarias,Canarias,Spain
,
Juan Manuel Alonso Dominguez
Affiliations:
Fundacion Jimenez Diaz,Madrid,Spain
,
Maria Isabel Montero
Affiliations:
Hematology,Hospital Universitario Virgen del Rocío de Sevilla,Sevilla,Spain
,
Maria Jose Lis Chulvi
Affiliations:
Consorcio Hospital General Universitario de Valencia,Valencia,Spain
,
Hanna Ciepłuch
Affiliations:
Hematology, Center of Oncology in Gdańsk,Gdańsk,Poland
Juan Luis Steegman
Affiliations:
Hematology,Hospital de la Princesa,Madrid,Spain
EHA Library. Garcia-Gutierrez V. Jun 15, 2019; 266803; PS1186
Valentin Garcia-Gutierrez
Valentin Garcia-Gutierrez
Contributions
Abstract

Abstract: PS1186

Type: Poster Presentation

Presentation during EHA24: On Saturday, June 15, 2019 from 17:30 - 19:00

Location: Poster area

Background
Ponatinib has been established as an optimal salvage treatment option in chronic myeloid leukemia (CML) patients. Serious adverse events, mainly cardiovascular (CVS) events, have been related to ponatinib use at the standard dose (45 mg/day). Clinical trials are currently evaluating different dose schemes in order to answer whether dose modifications could diminish side effects while maintaining responses.

Aims
To evaluate the efficacy and safety of ponatinib treatment in the real life-setting.

Methods
We have performed an International observational retrospective study collecting information from CML patients treated with ponatinib between 2014 and 2018. The indication of ponatinib, as well as its dose schedule, was made according to the criterion of the attending physician. Molecular biology tests were performed according to ELN guidelines and BCR-ABL/ABL ratios were expressed as % IS in all centers. Treatment responses were calculated with the patients at risk at each specific time points. For progression free survival (PFS) calculation, progression was defined as transformation to the advances phases. For the event free survival (EFS), the events were treatment discontinuation due to any reason, progression or death. Data collection followed the local regulations for observational studies.

Results
73 CML patients treated with ponatinib according to clinical practice in Spain, Poland, and Argentina, were included in the study. Patients had received a median of 2.8 TKIs prior to ponatinib treatment, with a median time of 43 months from CML diagnosis to ponatinib start. Median age at diagnosis was 58 years and Sokal prognostic risk score was low, intermediate, high, and unknown in 28%, 21%, 31%, and 20% of the patients. Patients were treated while in chronic phase (84%), accelerated phase (10%), and blast crisis (6%). In total, 61% of the patients had cardiovascular risk factors at the time of starting ponatinib, 5 patients had suffered previous thrombosis, and 4 patients had a pathological ankle-brachial index. BCR-ABL mutations were present in 33 patients (23 of them harbored the T315I mutation). Ponatinib starting dose was 45mg, 30mg, and 15mg in 60%, 20%, and 20% of the patients, respectively. Drug dosage was diminished in 21/45 (46%) of the patients who started on 45mg/day and in 4/14 (28%) patients who started on 30mg/day. In contrast, 50% (7/14) of the patients who started on ponatinib 15mg/day increased dose during follow up. Rates of Complete hematological responses, complete cytogenetic responses, and major molecular responses by 12 months (table 1) were 100%, 52%, and 45% respectively. Overall, 56% of patients improved previous response, 32% maintained the same degree of response, whereas 12% lost the baseline responses. With a median follow-up of 24 months, 35 patients (48%) discontinued treatment due to toxicity (38%), stem cell transplantation (21%), death (17%) or lack of efficacy (24%). Most frequent toxicities leading to treatment discontinuations were severe cardiovascular events, hepatotoxicity, and myelotoxicity (table 2). Severe cardiovascular events were seen in 10 patients (9%). The majority of patients (70%) experiencing cardiovascular events had more than 2 CVS risk factors before ponatinib start. EFS, PFS, and overall survival was 46%, 69% and 83% at 21 months.

Conclusion
The present study demonstrates that the use of ponatinib in daily clinical practice under a dose limiting strategy in responding patients appears to be safe and preserves its clinical efficacy.

Session topic: 8. Chronic myeloid leukemia - Clinical

Keyword(s): Chronic myeloid leukemia, Therapy, Tyrosine kinase inhibitor

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