Author response for "A SCORING SYSTEM TO PREDICT THE RISK OF ATRIAL FIBRILLATION IN CHRONIC LYMPHOCYTIC LEUKEMIA"

e19508 Background: With the increased use of novel agents like Bruton tyrosine kinase inhibitors (BTKi) for the treatment of chronic lymphocytic leukemia (CLL), the incidence of atrial fibrillation (AF) is on the rise in these patients. However, the excess burden added by AF to the morbidity and mortality of CLL patients is unclear. Methods: Using the appropriate ICD-9 and ICD-10 codes, the National Inpatient Sample (NIS) database was accessed to gather data of hospitalized CLL patients with AF from 2008 to 2019. Propensity-score matching (PSM) and logistic regression model were performed to control for baseline patient factors like age, sex, income, and the relevant co-morbidities to match 7265 CLL patient admissions with AF and 7265 CLL patient admissions without AF. The primary outcome was all-cause mortality (ACM), while secondary outcomes included stroke, acute heart failure (AHF), and total cost of hospital stay. Results: The mean age of the cohorts was 82 years. Females made up 44% of both groups. The AF group had similar prevalence of systemic hypertension (62.38% vs 62.10%; p= 0.73), diabetes mellitus (5.09% vs 5.43%; p= 0.35), congestive heart failure (5.57% vs 5.36%; p= 0.58), valvular heart disease (1.17% vs 1.44%; p= 0.14), and pulmonary hypertension (0.21% vs 0.14%; p= 0.31) compared to the group without AF. PSM revealed CLL patients with AF had a higher rate of ACM (6.06% vs 4.47%; p= <0.0001), AHF (7.50% vs 3.85%; p= <0.001), and stroke (3.09% vs 1.65%; p= <0.0001). Admission in the AF group also had a higher median total cost of hospital stay ($9097 vs $7646). A logistic regression model was done to adjust for confounders which revealed similar results for the AF group with increased adjusted odd’s ratio (aOR) of ACM (aOR:1.39, 95% confidence interval (CI): 1.19-1.61; p= <0.001), AHF (aOR: 2.16, 95% CI: 1.85-2.52; p= <0.001), and stroke (aOR:1.94, 95% CI: 1.54-2.44; P= <0.001) (Table). Conclusions: Our data suggest that hospitalized CLL patients with AF are at a significantly increased risk of all-cause mortality, AHF, and stroke. Several limitations like the inability to establish the temporal relationship between CLL and AF and the lack of data regarding medications of individual patients are important to keep in mind while interpreting the results.[Table: see text]

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CLO19-024: Risk of Atrial Fibrillation and Pulmonary Toxicities in Patients With Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma Treated With Ibrutinib

Journal of the National Comprehensive Cancer Network ◽

10.6004/jnccn.2018.7158 ◽

2019 ◽

Vol 17 (3.5) ◽

pp. CLO19-024

Author(s):

Nimesh Adhikari ◽

Myo H. Zaw ◽

Sriman Swarup ◽

Anita Sultan ◽

Upama Sharma ◽

...

Keyword(s):

Atrial Fibrillation ◽

Relative Risk ◽

Side Effects ◽

Chronic Lymphocytic Leukemia ◽

B Cell ◽

Respiratory Infections ◽

Meta Analysis ◽

Lymphocytic Leukemia ◽

Phase Iii ◽

Small Lymphocytic Lymphoma

Background: Bruton’s tyrosine kinase (BTK), a kinase downstream of the B-cell receptor, involves in the B cell survival and proliferation and has become an attractive therapeutic target. Ibrutinib is an oral potent, covalent inhibitor of BTK and hence employed in many hematologic malignancies. We performed a systematic review and pooled analysis of randomized controlled trials (RCTs) to determine the risk of atrial fibrillation (AF) and pulmonary toxicities among patients treated with ibrutinib. Methods: We performed a comprehensive literature search using MEDLINE, EMBASE databases, and meeting abstracts through September 2018. Phase 3 RCTs that mention AF and pulmonary toxicities as adverse effects were incorporated in the analysis. Mantel-Haenszel method was used to calculate the estimated pooled risk ratio with 95% CI. Random effects model was applied. Results: 4 phase III RCTs with a total of 1,383 patients with chronic lymphocytic leukemia or small lymphocytic lymphoma were eligible. Studies comparing Ibrutinib (I) vs ofatumumab, I vs chlorambucil, I+ bendamustine (B)+ rituximab (R) vs placebo + B+ R, and I vs R were included in the analysis. The AF incidence was 41 (5.686%) in the ibrutinib group vs 8 (1.208%) in the control arm. The relative risk (RR) for AF was statistically significant at 3.825 (95% CI: 1.848–7.917; P<.0001) and RD was 0.041 (95% CI: 0.023–0.059; P<.0001). The RR of all-grade side effects was as follows: cough, 1.133 (95% CI: 0.724–1.773; P=.584); edema, 1.375 (95% CI: 0.943–2.006; P=.098); pneumonia, 1.227 (95% CI: 0.884–1.703; P=.221); and upper respiratory infections (URI), 1.075 (95% CI: 0.809–1.429; P=.616). The RR of high-grade side effects was as follows: cough, 0.373 (95% CI: 0.063–2.209; P=.277); edema, 1.232 (95% CI: 0.199–7.649; P=.822); pneumonia, 1.277 (95% CI: 0.847–1.926; P=.243); and URI, 1.555 (95% CI: 0.239–10.127; P=.644). Conclusion: Our meta-analysis demonstrated that patients on ibrutinib noted a significant increase in the risk of atrial fibrillation with a relative risk of 3.825. However, the risk of pulmonary toxicities was not statistically increased in the ibrutinib group.

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