Iclusig (ponatinib)

In contrast, imatinib showed no overlap with these 81 genes under the same cross-dataset analysis framework. Cardiotoxicity-relevant functions were represented by directionally consistent genes linked to cardiac repolarization-associated ion handling (KCNN3), insulin-responsive metabolic regulation (FOXO1, HK2), cyclic adenosine monophosphate (cAMP)-responsive stress signaling (RAPGEF3), and mitochondrial homeostasis and redox regulation (MCL1, GCH1). Collectively, these results define a ponatinib-associated transcriptomic signature and nominate cross-dataset transcript-level candidates for subsequent mechanistic and experimental validation in ponatinib-associated cardiotoxicity.

These findings identify inflammation-induced pyroptosis as a central driver of the pathological changes in PON-induced cardiotoxicity. Notably, our work highlights BMP-7's capacity to inhibit these disease-related alterations. Collectively, these results expand on the current knowledge of the mechanistic framework of PON-induced cardiotoxicity, while also emphasizing BMP-7 as a promising therapeutic candidate with potential translational relevance.

Second-generation and third-generation TKIs further improved outcomes by targeting most imatinib-resistant mutations, with ponatinib-based regimens achieving deep molecular responses and long-term survival in most patients. Concurrently, immunotherapies like blinatumomab and CAR-T cells have enabled potent chemotherapy-free strategies, yielding high molecular response rates and challenging the necessity of allo-HSCT for all patients. Current evidence supports reserving allo-HSCT for high-risk patients, while those with sustained minimal residual disease (MRD) negativity may be cured with TKI and immunotherapy alone. Future progress hinges on optimizing combinations, integrating novel agents like asciminib and venetoclax, and leveraging MRD and genomic profiling for precision medicine.

There was no evidence of systemic toxicity or organ dysfunction after treatment. These findings demonstrated that PEG-pRAPA is an effective polymeric drug and drug delivery platform and support the hypothesis that nanoparticle-based pharmacotherapy can be an effective treatment strategy for VMs.

P2, N=80, Not yet recruiting, University of Alberta | Initiation date: Mar 2026 --> Jul 2026

BCR::ABL1 e6a3 demonstrated enhanced sensitivity to active-state selective inhibitors dasatinib and bosutinib, whereas BCR::ABL1 e6a3/T315I remained resistant. These data show that treatment with asciminib and ponatinib can select for mutations with notably elevated enzymatic activity, effectively targeted by an axitinib-based triple combination. These data highlight the remarkable mutability of the BCR::ABL1 kinase, including through novel isoforms and provides a strong rationale for the clinical assessment of a triple inhibitor combination as a strategy to overcome resistance to dual ponatinib and asciminib therapy.

This led to development of tyrosine kinase inhibitors (TKIs) such as Imatinib, Nilotinib, and Ponatinib. Asciminib does not appear to induce a prothrombotic or proinflammatory state under the conditions studied, which may be advantageous for CML patients. However, the observed increase in thrombin generation over time suggests a potential effect on secondary haemostasis that warrants further investigation in controlled studies.

Therefore, blocking BCR-ABL1, or its downstream C/EBPβ, TGF-β and arginase with inhibitors or shRNAs rescued T cell suppression by neutrophil-like CML cells. Accordingly, combination treatment with targeted therapy using ponatinib and immunotherapy with anti-PD1 antibody not only provides rapid remission, but also delayed relapses after treatment discontinuation, justifying combination treatment for TFR of CML.

P2, N=4, Terminated, M.D. Anderson Cancer Center | N=26 --> 4 | Trial completion date: Oct 2026 --> Apr 2026 | Active, not recruiting --> Terminated | Trial primary completion date: Oct 2026 --> Apr 2026; < 75% participation

TKI-associated bone marrow aplasia has been reported with agents such as imatinib, dasatinib, and nilotinib. This case supports the potential role of ponatinib as an effective salvage option following severe TKI-related marrow toxicity, particularly in patients who are not candidates for allogeneic transplantation. Further clinical experience and larger studies are needed to better define optimal management strategies for this rare but serious complication.

P1, N=56, Not yet recruiting, Sun Pharmaceutical Industries Limited

During follow-up, improvements in tricuspid regurgitant pressure gradient, brain natriuretic peptide values, and hypertension were observed after reducing the dose of the same TKI, interrupting the TKI treatment, and switching from the newer-generation TKIs to imatinib (IM) or bosutinib (BOS). These findings highlight the importance of blood pressure control and cardiovascular monitoring for CVE prevention in high-risk CML patients. Switching to IM or BOS, TKI dose reduction, or treatment discontinuation was observed to be associated with improvement in cardiovascular parameters in selected patients achieving deep molecular response.