Cardiovascular Events and Management Strategies Including Tyrosine Kinase Inhibitor Switching, Dose Reduction, and Discontinuation in Chronic Myeloid Leukemia: A Single-Center Retrospective Study

Figures

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  Figure 1. Estimated 10-year cardiovascular disease risk for the 63 patients Using the Suita score [14], SCORE2 [15], and SCORE2-OP [16] risk charts, cardiovascular disease risk was evaluated, and 63 patients were classified into three risk categories: low (green), intermediate (yellow), and high (red). The unique patient number (UPN) corresponds to the 63 CML patients included in this study. Risk categories were defined according to published guideline thresholds for each scoring system.

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  Figure 2. Detailed clinical course of the 63 patients under TKI treatment The bar graph shows treatment history with TKIs and the onset rate of CVEs in each patient with CML-CP. The X-axis is the observation period (month), and the Y-axis is the unique patient number (UPN). The clinical course of the following patients is shown: one patient who discontinued TKI because of severe CVE (UPN: 1), seven stopped TKIs after achieving long-term DMR (UPN: 2-8), 16 who discontinued TKIs because of adverse events other than CVEs (UPN: 9-24), and 39 who continued TKIs (UPN: 25-63). Imatinib treatment duration is shown in sky blue; dasatinib treatment duration, yellow; nilotinib treatment duration, orange; bosutinib treatment duration, medium slate blue; ponatinib treatment duration, magenta; treatment duration other than TKIs, gray; TFR duration referring to DMR, green; duration of TKI discontinuation because of adverse events other than CVEs, yellow-green; duration of TKI discontinuation because of CVEs, black; duration of abnormal finding occurrence on cardiovascular examination and of subclinical cardiovascular abnormality onset, red; and duration of severe CVE onset in violet stripe, triangle.…

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  Figure 3. Changes in the indicators for cardiotoxicity during TKI treatment The figure illustrates changes in tricuspid regurgitant pressure gradient (TRPG; reference value <30 mmHg), brain natriuretic peptide (BNP; reference value <100 pg/mL), and systolic and diastolic blood pressure before and after tyrosine kinase inhibitor (TKI) switch/reduction and TKI discontinuation. Red lines indicate worsening, defined as a transition from normal to abnormal values (TRPG ≥30 mmHg, BNP ≥100 pg/mL, or development of hypertension defined as systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg). Blue lines indicate improvement, defined as a transition from abnormal to normal values. “Pre” refers to measurements obtained immediately before the TKI modification, and “Post” refers to measurements obtained after switching, dose reduction, or discontinuation. A) The transtricuspid pressure gradient: TRPG data on 19 patients are available, and changes in their TRPG levels are shown. Elevated TRPG returned to normal in UPN: 41, 40, and 12. TRPG increased from the normal to high levels in UPN: 7, 26, 40, and 18. B) Brain natriuretic peptide (BNP): BNP data on 19 patients are available,…

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  Figure 4. Control of cardiotoxicities via discontinuing/switching TKI in three representative cases The X-axis indicates time in years from the initiation of TKI therapy. A) UPN 1: Dasatinib was initiated as a second-line treatment but was switched to nilotinib because of pleural effusion. However, nilotinib was also discontinued because of myocardial damage. The patient achieved MR 4.5 at the time of nilotinib discontinuation. DMR has been maintained without TKI re-administration. B) UPN 7: MR 4.5 was achieved after the initial treatment with dasatinib. However, this drug was reduced and discontinued because of pleural effusion and elevated BNP. Subsequently, such symptoms improved. MR 4.5 has been maintained without TKI readministration. C) UPN 12: MR 4.5 was achieved after the initial treatment with dasatinib. However, this drug was switched to bosutinib because of elevated BNP. MR 4.0 was maintained, and BNP became normal. No other CVEs were observed.