Session: 642. CLL: Therapy, excluding Transplantation: Poster I
Hematology Disease Topics & Pathways:
Leukemia, Adult, Diseases, CLL, Elderly, Adverse Events, Lymphoid Malignancies, Study Population, Clinically relevant
Three hundred and one patients with CLL were included in this analysis. Patients were participants enrolled on ibrutinib-based clinical trials from 2010 to 2017. Collected information included patient demographics, comorbidities, tobacco use, and antihypertensive therapy. BP was evaluated at baseline, at 1 month, then every 3 months for one year followed by every 2 years for a total of 5 years. Development of HTN was characterized as a systolic BP (SBP) of ≥ 130 mmHg and/or diastolic BP (DBP) ≥ 80 mmHg on two separate visits with no prior diagnosis of HTN or use of antihypertensive therapy. We also recorded any change in systolic or diastolic BP ≥10 mmHg. Univariate logistic regression and linear regression analysis was performed to assess the relationship of HTN risk factors and new or worsened HTN.
Patients’ characteristics are described in the table 1 below. Median follow-up was 3 years (range 3 months-5 years). Pre-existing HTN was present in 68% of patients, and 47% were on antihypertensive therapy prior to ibrutinib. New HTN developed in 71% of patients without prior diagnosis of HTN. Worsening HTN developed in 56% of patients who had HTN at baseline. However, only 37% of them were started on antihypertensive therapy or received additional antihypertensive therapy. Of the patients who experienced an increase in BP, 29% experienced isolated systolic HTN. Median SBP was 131 mmHg at baseline, 132 mmHg at 1 month, 137 mmHg at 3 months, 137 mmHg at 6 months, 139 mmHg at 12 months, 140.5 mmHg at 3 years, and 139.5 mmHg at 5 years (mean increase in SBP: 8.15, 95% CI: 5.9 – 10.4). In patients whose SBP was < 130 mmHg at baseline the median SBP was 118 mmHg at baseline, 122.5 mmHg at 1 month, 131 mmHg at 3 months, 130 mmHg at 6 months, 134 mmHg at 12 months, 133.5 mmHg at 3 years and 138 mmHg at 5 years (mean increase in SBP: 17.3, p=0.001). Seventy-nine percent of patients experienced an increase in SBP ≥10 mmHg. The median time to onset of new or worsened HTN (50% cumulative incidence) was 12 months. New HTN on ibrutinib was not associated with tobacco use, obesity, chronic kidney disease, or obstructive sleep apnea (p > 0.05).
Development of cardiovascular and renal complications associated with HTN were also studied. New or worsening atrial fibrillation occurred in 17.3% of patients, new or worsening congestive heart failure in 3.0% of patients, new or clinically significant worse coronary artery disease was documented in 8.0% of patients, ischemic stroke occurred in 3.3% of patients and intracerebral hemorrhages occurred in 2.7% of patients. New or worsening chronic kidney disease was observed in 14.3% of patients.
Based on our findings, an increase in BP is common in patients with CLL being treated with long-term ibrutinib therapy. We observed that HTN in these patients is persistent, progressive and independent of other common risk factors for HTN. A proportion of patients developed cardiovascular complications during treatment and worsening renal function. Only 37% of patients in our study received new or additional antihypertensive medications, which may account for the persistent BP elevation and suggests a suboptimal HTN management in these patients.
Disclosures: Burger: Pharmacyclics, an AbbVie company: Consultancy, Research Funding, Speakers Bureau; Janssen Pharmaceuticals: Consultancy, Speakers Bureau; Gilead Sciences: Consultancy, Research Funding; Beigene: Research Funding, Speakers Bureau; AstraZeneca: Consultancy; TG Therapeutics: Research Funding, Speakers Bureau. Jain: TG Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Precision Bioscienes: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BeiGene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Incyte: Research Funding; Servier: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Research Funding; ADC Therapeutics: Research Funding; Cellectis: Research Funding; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Research Funding; Verastem: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Adaptive Biotechnologies: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Fate Therapeutics: Research Funding; AstraZeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Aprea Therapeutics: Research Funding.
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