imatinib

Multi-target agents are no longer constrained by single-target effects; however, issues of balanced potency, ADMET, and control still exist. The combination of AI, quantum computing, and precision polypharmacology may enable more effective multi-target interventions to address unmet demands in complex diseases.

P4, N=250, Completed, Novartis Pharmaceuticals | N=155 --> 250

Imatinib 400 mg daily was initiated but was replaced with dasatinib 100 mg daily because of intolerance. This case highlights the diagnostic complexity of synchronous hematologic malignancies and the importance of comprehensive multimodal evaluation when clinical, morphologic, and laboratory findings are not fully explained by a single diagnosis. Treating the clinically dominant clone while monitoring the second clone may be appropriate when the latter is asymptomatic.

In a genetically engineered murine GIST model, PD-L1 blockade enhanced imatinib efficacy and restored tumor γδ T cell function. Thus, γδ T cells contribute to tumor immunity in GIST and are reprogrammed during imatinib resistance, making them an attractive immunotherapy target.

High-level evidence, including prospective interventional studies, supports exposure-guided dosing for imatinib and sunitinib, demonstrating improved molecular or clinical outcomes when predefined trough concentration targets are achieved. For alectinib, cabozantinib, trametinib, and lenvatinib, consistent exposure-response or exposure-toxicity relationships and pragmatic concentration thresholds support selective implementation, although randomized validation remains limited. For agents such as osimertinib, brigatinib, olaparib, and niraparib, monitoring appears most clinically relevant in toxicity-driven scenarios rather than for efficacy optimization. In contrast, lorlatinib currently lacks a clearly defined therapeutic window, limiting routine applicability...In conclusion, therapeutic drug monitoring and model-informed precision dosing are ready for selective clinical adoption in a subset of oral targeted therapies. Future prospective trials integrating pharmacometric tools with patient-centered outcomes are required to refine exposure targets and expand evidence-based implementation.

Lastly, our biochemical data were validated using imatinib response data for first-line metastatic disease; patients with predicted exon 18 sensitive mutations had longer progression-free survival than patients with predicted imatinib-resistant mutations. These results provide key evidence that should be used to guide therapy selection for PDGFRA-mutant GIST.

Among patients with chronic myeloid leukemia (CML) aiming for tyrosine kinase inhibitor (TKI) discontinuation, second-generation TKIs (2G-TKIs) are used as one of the first-line options because they induce faster and deeper molecular responses than imatinib...We analyzed 431 patients enrolled in the phase III Japan Adult Leukemia Study Group (JALSG) CML212 trial, comparing nilotinib at 300 mg twice daily (n = 218) and dasatinib at 100 mg once daily (n = 213) as first-line therapy...In multivariable models, HT(0-3) (subdistribution hazard ratio [HR], 2.23; 95% CI, 1.09-4.55) and the 6-month IS (HR, 0.38; 95% CI, 0.31-0.47) were independent predictors of MR4.5 attainment, whereas only the 6-month IS predicted TDE (odds ratio, 0.37; 95% CI, 0.24-0.56). This study demonstrates that molecular response at 6 months after TKI initiation has important clinical value in early stratification of MR4.5 attainment and TDE in patients receiving 2G-TKI therapy.

Chronic lymphocytic leukaemia (CLL) most commonly transforms into aggressive lymphoma; development of chronic myeloid leukaemia (CML) in a patient with CLL should prompt evaluation for an independent myeloid clone rather than presumed transformation.Myeloid neoplasms in patients with CLL may arise from therapy-related leukemogenesis or divergent evolution from a shared hematopoietic progenitor, highlighting the importance of molecular characterization.Management of coexisting CLL and CML requires individualized risk-benefit assessment, particularly in elderly patients with prior solid tumours and immune dysfunction.

Adjuvant tyrosine kinase inhibitors, such as imatinib, are reserved for high-risk lesions or unresectable tumors. This case highlights the importance of considering GIST as a differential diagnosis in obscure upper GI bleeding. It also demonstrates that laparoscopic resection is a safe and effective treatment option for ileal GISTs, even in the context of acute bleeding.

For therapeutic categories, performance reached 0.84 for avapritinib sensitivity and 0.81 for imatinib sensitivity. Prognostic performance was comparable to pathology-based scores, with highest discrimination in the overall cohort and in patients without adjuvant therapy. DL applied to WSIs enables prediction of molecular alterations, treatment sensitivity, and RFS in GIST, performing comparably to established risk scores across international cohorts, providing a baseline for future multimodal predictors.

The study also showed the inherent resistance of the KIT p.Ala829Pro mutation to imatinib, explaining the failure of subsequent treatment. This study highlights the significant spatial and temporal heterogeneity of acral melanoma and underscores the critical importance of serial biopsies in accurately capturing clonal dynamics and guiding precision oncology therapy.