5-year study of the effect of cardiac monitoring on the overall survival of patients with chronic lymphocytic leukemia receiving targeted therapy with ibrutinib

Abstract

Aim To evaluate the effect of cardiac monitoring on overall survival of patients with chronic lymphoid leukosis (CLL) on targeted therapy with ibrutinib.Material and methods Survival of oncological patients depends not only on the efficacy of the antitumor therapy. Cardiovascular comorbidities and emerging cardiotoxicity of the antitumor treatment can considerably impair the quality and duration of patients’ life. The problem of the need for regular cardiological monitoring of oncological patients remains unsolved. A prospective 5-year study was performed that included cardiological monitoring of patients with CLL on chronic targeted therapy with ibrutinib, the side effects of which include atrial fibrillation (AF) and arterial hypertension (AH). The study included 217 patients aged 66.0 [32.0; 910.] years; 144 of them were men aged 66.0 [32.0; 91.0] years and 83 were women aged 65.0 [39.0; 83.0] years. Electrocardiography and echocardiography, evaluation of comorbidity with the Charlson’s index, and evaluation of frailty with the Geriatric 8 questionnaire and the Groningen Frailty Index were performed repeatedly for all patients. In the active cardiac monitoring group (n=89), besides the standard evaluation, active medical monitoring of symptoms and general well-being, blood pressure (BP) and pulse rate, monitoring of cardioprotective drug intake and correction, if necessary, and calling patients for examination and additional evaluation were performed every week. The remaining 128 patients were evaluated repeatedly but did not maintain the remote monitoring with messengers; they constituted a standard follow-up group.Results This was a study of overall survival of patients with CLL on targeted therapy with ibrutinib depending on the cardiac monitoring program. The age of patients did not differ in the active cardiac monitoring group and the standard follow-up group (66.0 [60.0; 70.0] and 66.0 [59.0; 74.0] years, respectively). The active cardiac monitoring group contained somewhat more men than the standard follow-up group (68.8 and 53.9 %, respectively; р=0.026). At baseline, the groups did not differ in the number of pretreatment lines, frailty test results (Geriatric 8 questionnaire, Groningen Frailty Index), comorbidity (Charlson’s index), and echocardiographic data. The active cardiac monitoring group contained more patients with AH (р<0.0001), with AF (р<0.0001), patients receiving anticoagulants (р<0.0001), and a comparable number of patients with ischemic heart disease. In the active cardiac monitoring group, 70 (90.9%) of 77 patients with CLL and AH achieved goal BP whereas in the standard follow-up group, 26 (39.9 %) of 66 (р<0.0001) patients achieved the BP goal, regardless of whether their elevated BP developed before or during the ibrutinib treatment. This group contained significantly more patients who required cardiac surgical intervention (coronary stenting, pacemaker implantation), 12 vs. 0 in the standard follow-up group (р=0.0004). The overall 5-year survival was significantly higher for patients of the active cardiac monitoring group, both for men (р<0.0001) and women (р<0.0001) with CLL, including patients older than 70 years (р=0.0004), CLL patients with a median pretreatment line number of 1 (р<0.0001), patients with a median chemotherapy line number of 4 (р<0.0001), and patients with genetic abnormalities (р=0.004) pretreated with fludarabine and/or anthracyclines (р<0.0001). The Cox regression analysis showed that the strongest predictor of survival was the achievement of stable goal BP in CLL patients with AH during the continuous cardiac monitoring. Despite more pronounced cardiac comorbidity, CLL patients on the active cardiac monitoring group showed a longer survival than patients on the standard follow-up. Thus, mean survival time of deceased CLL patients who had been on the cardiac monitoring was 36.1 months vs. 17.5 months (р<0.0001) for patients who had been on the standard follow-up.Conclusion The study has demonstrated the prognostic significance of continuous participation of a cardiologist in managing onco-hematological patients. CLL patients on the active cardiac monitoring, the regular pattern of which was provided by the remote control, had a significantly higher overall survival compared to patients who visited a cardiologist periodically. A significant predomination of patients with CLL and AH who achieved stable goal BP, continuous monitoring of anticoagulant dosing in patients with AF in that group, and early detection and correction of cardiovascular complications can explain the highly significant difference in the 5-year survival between CLL patients on chronic targeted ibrutinib treatment with different cardiac monitoring programs (р<0.0001). The active cardiac monitoring with remote control allows achievement of a higher 5-year overall survival of CLL patients receiving ibrutinib (p<0.0001).