imatinib

P2, N=222, Recruiting, National Cancer Institute (NCI) | Phase classification: P3 --> P2

Intermediate A demonstrated superior antiproliferative activity compared to derivatives 1-12 and exhibited cytotoxicity comparable to imatinib in K562 cells (IC50 = 6.15 ± 1.26 µM vs. 5.14 ± 1.44 µM, respectively)...The compound showed acceptable predicted physicochemical and ADME characteristics based on in silico analysis. Intermediate A emerges as a significant anti-CML candidate exhibiting potent cytotoxic, apoptotic, and moderate ABL TK inhibitory activity, together with a favorable selectivity profile.

The cumulative risk score based on m6A pathway variants showed a strong association with PFS. These findings provide preliminary, hypothesis-generating evidence that genetic variations may contribute to inter-patient variability in outcomes and warrant further investigation as potential biomarkers in IM-treated GIST.

A literature review of all children with PDGFRB rearrangement was collated in our analysis. The challenges of diagnosis, treatment, and follow-up posed by such a rare genetic disorder with no pediatric guidelines are being discussed.

P1, N=18, Recruiting, University of California, San Diego | Not yet recruiting --> Recruiting | Initiation date: Dec 2025 --> Jun 2026

P2, N=125, Active, not recruiting, University of Jena | Not yet recruiting --> Active, not recruiting

P3, N=21, Terminated, University of Maryland, Baltimore | Completed --> Terminated; The Principal Investigator left the institution. The study was halted prematurely.

P2, N=45, Not yet recruiting, The University of Hong Kong

The median overall survival of 5 patients with available follow-up was 11 months. We conclude that the reciprocal translocation t(5;12)(q32;p13) requires a careful and step-wise diagnostic work-up to differentiate between an underlying ETV6::PDGFRB fusion gene with associated excellent prognosis on imatinib and an ETV6::ACSL6 fusion gene, for which the prognosis is poor and alloHCT appears to be a promising therapeutic option.

All TKIs are not recommended during the first trimester due to their risk of teratogenesis, but imatinib and nilotinib may be cautiously used from Weeks 16-18 onward. Non-TKI therapies, such as hydroxyurea and interferon-α, are considered safe throughout pregnancy. Data on ponatinib and asciminib remain insufficient to allow the safe use of these agents during pregnancy. Future research should aim to improve treatment-free remission rates through novel agents and combination strategies to allow a higher proportion of younger patients to discontinue therapy. Clinicians should always counsel women on pregnancy risks during therapy while reassuring male patients of TKI safety when fathering children.

We report that imatinib-treated neutrophils can process and release IL-1β independently of NLRP3 inflammasome assembly and the expression/activity of caspase-1 or Gasdermin D. Mechanistically, imatinib induces azurophilic granule permeabilization to drive robust cytosolic accumulation of granule-derived neutral serine proteases, serine protease-mediated processing of proIL-1β, and release of mature IL-1β. Together these findings elucidate a novel mechanism by which disruption of neutrophil granules can bypass the NLRP3 inflammasome pathway to drive serine protease-mediated IL-1β processing and release.

Notably, during treatment with tyrosine kinase inhibitors (TKIs), she became intolerant to first- and second-generation TKIs, including the branded and generic imatinib, nilotinib, and dasatinib, followed by progression into lymphoid blast phase. This case highlights the diagnostic challenges and therapeutic complexity of managing CML in the setting of multi-TKI intolerance. Importantly, it underscores the persistent molecular silence despite repeated RT-qPCR testing and the successful introduction of asciminib as a novel therapeutic alternative.