Tyrosine Kinase Inhibitor Dosing Patterns in Elderly Patients With Chronic Myeloid Leukemia

Seo, Hyungjoon; Ko, Tae Hwa; Hyun, Shin Young; Song, Hyebin; Lim, Seung Taek; Shim, Kwang Yong; Lee, Jong In; Kong, Jee Hyun

doi:10.1016/j.clml.2019.08.009

Cited by 5 publications

(3 citation statements)

References 34 publications

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“…The feasibility of RD-TKIs has been reported also in elderly patients [ 4 , 11 , 14 , 26 , 35 , 36 ]. For instance, Seo et al conducted a comprehensive analysis of TKI dosing patterns in a cohort of 378 patients with a median age of 75 years, revealing that RD-TKIs were administered in 65.9% of patients at the latest follow-up, with no discernible impact on the OS [ 37 ]. In our cohort, 36.5% of patients started treatment with RD-TKIs, while the proportion of patients receiving RD-TKIs had increased to >60% in the second line and in all the patients in the subsequent lines.…”

Section: Discussionmentioning

confidence: 99%

Safety and Efficacy of TKIs in very Elderly Patients (≥75 Years) with Chronic Myeloid Leukemia

Costa,

Abruzzese,

Latagliata

et al. 2024

JCM

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Background: While the outcomes of chronic phase chronic myeloid leukemia (CP-CML) patients aged over 65 years have been extensively evaluated in real-life experiences, limited data exist for the very elderly population (i.e., aged ≥ 75 years), especially for next-generation tyrosine kinase inhibitors (TKIs). In this retrospective study, we sought to evaluate the safety and efficacy of TKIs in this particular setting of patients. Methods: We conducted a retrospective analysis of a multicenter cohort of 123 newly diagnosed CP-CML very elderly patients. Results: The median age at diagnosis was 80 years (range: 75–96). In the first line, 86.1% of patients received imatinib, 7.1% dasatinib, 5.6% nilotinib, and 0.81% received bosutinib. A total of 31 patients (25.2%) switched to second-line therapy, nine patients to a third line, and one patient to a fourth line of therapy. Resistance to treatment was the primary reason for switching therapy in both the first (64.5%) and second lines (77.7%). At diagnosis, reduced doses were administered in 36.5% of patients, in 61.2% in the second line, and in all patients in subsequent lines of therapy. In the first-line setting, 71.9% of patients achieved an early molecular response (EMR, i.e., 3-month BCR::ABL1IS < 10%); at 6, 12, and 24 months, MR3 was reached by 35.7%, 55.7%, and 75.0% of patients, respectively, with 16.6%, 35.7%, and 51.7% achieving a deep molecular response (DMR) at the same time points. Treatment-free remission (TFR) was successfully attempted in 11 patients. During the follow-up period, adverse events (AEs) were observed in 78.8% of patients, including 22 cases of cardiovascular AEs. Toxicity grade ≥ 3 was more commonly observed in patients treated with standard doses of TKIs compared to reduced doses (p = 0.033). Overall, the median follow-up was 46.62 months (range: 1.8–206.2), and 43 patients died due to non-CML-related causes. Three patients died due to disease progression to advanced (n = 1) and blastic (n = 2) phases. The 5-year overall survival (OS) for the entire cohort was 71.9% (95% CI: 0.63–0.81), with no significant difference between the patients treated with standard doses of TKIs compared to those treated with reduced doses (p = 0.35). Conclusions: TKIs appear to be safe and effective even in very elderly CML patients, and dose optimization strategies yield satisfactory molecular responses for adequate disease control with an improved safety profile.

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Section: Discussionmentioning

confidence: 99%

Safety and Efficacy of TKIs in very Elderly Patients (≥75 Years) with Chronic Myeloid Leukemia

Costa,

Abruzzese,

Latagliata

et al. 2024

JCM

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“…Several studies have shown that TKI treatment is effective and well tolerated in all age groups. Therefore, age-related biological differences do not seem to affect the prognosis of CML in the elderly [ 37 , 38 , 39 , 40 ].…”

Section: Introductionmentioning

confidence: 99%

Potential to Improve Therapy of Chronic Myeloid Leukemia (CML), Especially for Patients with Older Age: Incidence, Mortality, and Survival Rates of Patients with CML in Switzerland from 1995 to 2017

Daskalakis

Feller

Noetzli

et al. 2021

Cancers

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Background: Tyrosine kinase inhibitors (TKI) substantially improved chronic myeloid leukemia (CML) prognosis. We aimed to describe time period- and age-dependent outcomes by reporting real-world data of CML patients from Switzerland. Methods: Population-based incidence, mortality, and survival were assessed for four different study periods and age groups on the basis of aggregated data from Swiss Cantonal Cancer Registries. Results: A total of 1552 new CML cases were reported from 1995 to 2017. The age-standardized rate (ASR) for the incidence remained stable, while the ASR for mortality decreased by 50–80%, resulting in a five-year RS from 36% to 74% over all four age groups. Importantly, for patients <60 years (yrs), the five-year RS increased only in earlier time periods up to 92%, whereas for older patients (+80 yrs), the five-year RS continued to increase later, however, reaching only 53% until 2017. Conclusions: This is the first population-based study of CML patients in Switzerland confirming similar data compared to other population-based registries in Europe. The RS increased significantly in all age groups over the last decades after the establishment of TKI therapy. Interestingly, we found a more prominent increase in RS of patients with older age at later observation periods (45%) compared to patients at younger age (10%), implicating a greater benefit from TKI treatment for elderly occurring with delay since the establishment of TKI therapy. Our findings suggest more potential to improve CML therapy, especially for older patients.

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“…The Torin-2 is considered as a kinase inhibitor which worked in the PI3K-Akt/mTOR signaling pathway 117,119,122 , which supports our previous pathway analysis for the hub proteins. Radotinib (IY-5511) were being prescribed for the chronic myeloid leukaemia (CML) 123,124 whereas Thiostrepton was used for acute kidney injury treatment 125 . The evidences show that the Tacrolimus has a positive inhibitory impact on the COVID-19 patients with comorbidities like kidney and liver transplantation 126,127 .…”

Section: Discussionmentioning

confidence: 99%

Computational identification of host genomic biomarkers highlighting their functions, pathways and regulators that influence SARS-CoV-2 infections and drug repurposing

Mosharaf

Reza

Kibria

et al. 2022

Sci Rep

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The pandemic threat of COVID-19 has severely destroyed human life as well as the economy around the world. Although, the vaccination has reduced the outspread, but people are still suffering due to the unstable RNA sequence patterns of SARS-CoV-2 which demands supplementary drugs. To explore novel drug target proteins, in this study, a transcriptomics RNA-Seq data generated from SARS-CoV-2 infection and control samples were analyzed. We identified 109 differentially expressed genes (DEGs) that were utilized to identify 10 hub-genes/proteins (TLR2, USP53, GUCY1A2, SNRPD2, NEDD9, IGF2, CXCL2, KLF6, PAG1 and ZFP36) by the protein–protein interaction (PPI) network analysis. The GO functional and KEGG pathway enrichment analyses of hub-DEGs revealed some important functions and signaling pathways that are significantly associated with SARS-CoV-2 infections. The interaction network analysis identified 5 TFs proteins and 6 miRNAs as the key regulators of hub-DEGs. Considering 10 hub-proteins and 5 key TFs-proteins as drug target receptors, we performed their docking analysis with the SARS-CoV-2 3CL protease-guided top listed 90 FDA approved drugs. We found Torin-2, Rapamycin, Radotinib, Ivermectin, Thiostrepton, Tacrolimus and Daclatasvir as the top ranked seven candidate drugs. We investigated their resistance performance against the already published COVID-19 causing top-ranked 11 independent and 8 protonated receptor proteins by molecular docking analysis and found their strong binding affinities, which indicates that the proposed drugs are effective against the state-of-the-arts alternatives independent receptor proteins also. Finally, we investigated the stability of top three drugs (Torin-2, Rapamycin and Radotinib) by using 100 ns MD-based MM-PBSA simulations with the two top-ranked proposed receptors (TLR2, USP53) and independent receptors (IRF7, STAT1), and observed their stable performance. Therefore, the proposed drugs might play a vital role for the treatment against different variants of SARS-CoV-2 infections.

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Tyrosine Kinase Inhibitor Dosing Patterns in Elderly Patients With Chronic Myeloid Leukemia

Cited by 5 publications

References 34 publications

Safety and Efficacy of TKIs in very Elderly Patients (≥75 Years) with Chronic Myeloid Leukemia

Safety and Efficacy of TKIs in very Elderly Patients (≥75 Years) with Chronic Myeloid Leukemia

Potential to Improve Therapy of Chronic Myeloid Leukemia (CML), Especially for Patients with Older Age: Incidence, Mortality, and Survival Rates of Patients with CML in Switzerland from 1995 to 2017

Computational identification of host genomic biomarkers highlighting their functions, pathways and regulators that influence SARS-CoV-2 infections and drug repurposing

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