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The immunological mechanism of treatment-free remission is not clearly understood. We aimed to identify immune-related genetic differences that predict molecular relapse after tyrosine kinase inhibitor (TKI) discontinuation in patients with chronic phase chronic myeloid leukemia (CML). In this prospective multicenter study, patients who were treated with TKI for at least 3 years discontinued TKI and were monitored for loss of major molecular response. We used NanoString profiling to find gene expression differences associated with relapse. From August 2019 to April 2020, 42 patients were enrolled from five centers in South Korea. During the median follow-up of 16.9 months, 47.6% (20/42) of patients experienced molecular relapse. The 6- and 12-month molecular relapse-free survival (RFS) rates were 52.5% and 50%, respectively. The e14a2 transcript type and longer duration (≥ 50 months) of deep molecular response before TKI discontinuation were associated with longer molecular RFS. NanoString analysis revealed significant differences in immune-related gene expression between relapsed and non-relapsed patients at the time of TKI discontinuation, including T cell-related genes such as SIGLEC1, ARG2, CD160, and IFNG. In conclusion, differences in expression of immune-related genes may provide a prognostic marker for relapse after TKI discontinuation in patients with CML.
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http://dx.doi.org/10.1007/s00277-025-06514-8 | DOI Listing |
Cancer Res Commun
September 2025
University of Tsukuba, Tsukuba, Japan.
Immune checkpoint inhibitor (ICI) combinations and tyrosine kinase inhibitor (TKI) use are standard for metastatic renal cell carcinoma (mRCC), leading to improved outcomes. However, due to a lack of predictive biomarkers, the presence or absence of immune-related adverse events (irAEs) is currently employed as a predictive factor in clinical practice. To elucidate the impact of irAEs on efficacy, a cohort of mRCC patients who received ICI-based combination therapy as initial treatment was analyzed.
View Article and Find Full Text PDFInt Urol Nephrol
September 2025
Department of Urology, Tokyo Women's Medical University, Tokyo, Japan.
Background: Data on the impact of first-line immune checkpoint inhibitor (ICI) combination therapy regimen on the outcomes of second-line tyrosine kinase inhibitor (TKI) treatment for advanced renal-cell carcinoma (RCC) remain limited.
Methods: We retrospectively evaluated data from 105 patients who discontinued first-line ICI combination therapy. Progression-free survival (PFS) after second-line TKI treatment and PFS2, defined as the sum of PFS during first-line and second-line therapies, were compared between patients who received dual ICI combination therapy (i.
J Manag Care Spec Pharm
September 2025
Division of Medical Oncology, Department of Medicine, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles.
Background: Alectinib, brigatinib, and lorlatinib are all preferred first-line (1L) therapies for anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) in National Comprehensive Cancer Network (NCCN) guidelines. Although clinical trials have demonstrated their efficacy, real-world evidence on treatment patterns, costs, and outcomes may help differentiate these therapies and inform optimal 1L treatment selection in the absence of head-to-head comparisons.
Objective: To evaluate real-world outcomes for patients with ALK+ NSCLC receiving 1L ALK tyrosine kinase inhibitors (TKIs), focusing on drug acquisition costs, health care utilization, and clinical outcomes.
Clin Lung Cancer
August 2025
Division of Oncology, Department of Medicine, Stanford University, Stanford, CA; Department of Medicine, VA Palo Alto Health Care System, Palo Alto, CA.
Purpose: EGFR-mutated (EGFRm) NSCLC is associated with high incidence of brain metastases and leptomeningeal disease (LMD), for which effective systemic options beyond osimertinib 80 and 160 mg daily are limited. While there is some evidence for high-dose pulse administration of earlier-generation EGFR tyrosine kinase inhibitors (EGFK-TKIs), data for pulse-dose osimertinib are limited.
Methods: This multicenter retrospective case series included patients with EGFRm NSCLC with LMD or parenchymal brain metastases treated with pulse-dose osimertinib (400-560 mg once every 5-7 days) for central nervous system (CNS) progression, with or without other concurrent therapies.
Hematol Rep
August 2025
Hospital Universitario de Gran Canaria Doctor Negrin (HUGCDN), 35019 Las Palmas de Gran Canaria, Spain.
: The advent of tyrosine kinase inhibitors (TKIs) revolutionized the management of chronic myeloid leukemia (CML), achieving survival rates near those of the general population. Despite this success, prolonged therapy presents challenges, including physical, emotional, and financial burdens. Treatment-free remission (TFR), defined as sustained deep molecular response (DMR) after discontinuing TKIs, has emerged as a viable clinical goal.
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