The Outcomes of Ponatinib Therapy in Patients With Chronic Myeloid Leukemia Resistant or Intolerant to Previous Tyrosine Kinase Inhibitors, Treated in Poland Within the Donation Program

• Published in: Clinical lymphoma, myeloma and leukemia myeloma and leukemia, 2022-06, Vol.22 (6), p.405-415
• Main Authors: Sacha, Tomasz, Szczepanek, Elżbieta, Dumnicka, Paulina, Góra-Tybor, Joanna, Niesiobędzka-Krężel, Joanna, Prejzner, Witold, Wasilewska, Ewa, Kłoczko, Janusz, Ciepłuch, Hanna, Makowska, Wioletta, Patkowska, Elżbieta, Wasilewska, Joanna, Bober, Grażyna, Kopera, Małgorzata, Wichary, Ryszard, Kroll-Balcerzak, Renata, Gromek, Tomasz, Wach, Małgorzata, Rudkowska-Kazanowska, Anna, Świniarska, Magdalena, Paczkowska, Edyta, Biernat, Monika, Joks, Monika, Oller, Marta, Kasza, Renata, Kostyra, Aleksandra, Gil, Justyna, Grzybowska-Izydorczyk, Olga
• Format: Article
• Language: English
• Subjects: Adult; Antineoplastic Agents - therapeutic use; CML; Drug Resistance, Neoplasm; efficacy and safety; Humans; Imidazoles; intolerance; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - genetics; Poland; Protein Kinase Inhibitors - adverse effects; Pyridazines; real-life data; resistance; Retrospective Studies; Third generation TKI
• ISSN: 2152-2650; 2152-2669
• DOI: 10.1016/j.clml.2021.11.012

Tyrosine kinase inhibitors (TKIs) have greatly improved the treatment outcome for most patients with chronic myeloid leukemia (CML). Ponatinib is a new pan-inhibitor of TK active in resistant CML. This study aimed to evaluate the efficacy and safety of ponatinib in patients suffering from CML. This multicenter, non-randomized, observational, retrospective study evaluated the efficacy and safety of ponatinib administered in adult CML patients in any disease phase, including those with a detected ABL T315I mutation, which were resistant or intolerant to previous-generation TKIs. The study comprised 43 patients benefiting from the ponatinib donation program who were treated in 16 Polish centers. For patients who started treatment with ponatinib in chronic phase (CP) (n = 23) and in accelerated phase (AP) (n = 3) the median time on ponatinib was 19.5 months (range: 1.0-35.4), and 31.7 months (range: 31.0-34.1), respectively. All these patients were in CP after 1 month of treatment and at the end of observation – none of them progressed to AP or blastic phase (BP) during the study, meaning that progression-free survival was 100% at the end of observation (35.4 months). The estimated 2-year survival in this group of patients was 84%. For all 43 patients, median survival was not reached (lower quartile 6.3 months), and estimated 2-year survival was 60%. Our analysis confirmed ponatinib efficacy in a significant proportion of patients heavily pre-treated with TKIs achieving durable responses in both CP and AP/BP CML groups. Ponatinib is a new pan-inhibitor of tyrosine kinase active in resistant chronic myeloid leukemia (CML). Evaluation of outcomes in 43 patients confirmed ponatinib efficacy in a significant proportion of subjects heavily pre-treated with tyrosine kinase inhibitors achieving durable responses in both chronic phase and accelerated/blastic phase CML groups.