Ponatinib in Chronic Myeloid Leukaemia Refractory To Multiple Tyrosine Kinase Inhibitors: Data from a Tertiary Care...

Allogeneic haematopoietic stem cell transplantation (HSCT) is currently indicated in Chronic Myeloid Leukemia (CML) patients who are intolerant or resistant to 2 or more Tyrosine Kinase Inhibitors (TKIs) or in patients with advanced stage disease. This study reports the use of ponatinib as a salvage option in patients who are either ineligible or cannot afford an allogenic transplant. CML patients treated with ponatinib at our centre between 1st January 2019 to 28th February 2025 were assessed retrospectively. The study included 40 patients [35 CML chronic phase (CP) and 5 CML- accelerated phase (AP) patients]. RQPCR data was available for 25 patients at three and twelve months, respectively. At 3 months, a total of 16 patients (64%) attained Early Molecular Response (EMR) (RQPCR ≤ 10%). Fifteen of these 25 patients (60%) attained a Complete Cytogenetic Response (CcyR) at 1 year. Out of the entire cohort, a total of 15 patients (41.66%) attained a Major Molecular Response (MMR) (RQPCR ≤ 0.1%) and 6 patients (16.66%) attained a Deep Molecular Response (DMR) (RQPCR < 0.01%). The median overall survival (OS) and progression free survival (PFS) was not reached for the cohort. Median OS at 2 and 4 years was 94.8% (95% CI 88-100), 88.5% (75.8-100) and the PFS in the study population at 1, 2 and 4 years were 71.9% (95% CI 58.4-88.5), 55.6% (95% CI 40-77.2) and 55.6% (95% CI 40-77.2) respectively. The most common grade 3/4 treatment emergent adverse events (TEAE) were thrombocytopenia (32.5%), anaemia (20%) and neutropenia (22.5%). Serious Adverse Events (SAE) including death, arterial occlusive events (AOE), cardiac adverse events and blast transformation occurred in 3 patients (7.5%), 3 patients (7.5%), 3 patients (7.5%) and 2 patients (5%) respectively. This retrospective analysis shows that ponatinib is an effective option in a subset of patients who have failed multiple lines of TKI or harbour T315I mutations or are transplant ineligible. The drug is associated with a considerable toxicity profile.

The online version contains supplementary material available at https://doi.org/10.1007/s12288-025-02184-8.