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. 2021 Jan;100(1):143-155.
doi: 10.1007/s00277-020-04094-3. Epub 2020 Jun 1.

Atrial fibrillation in patients with chronic lymphocytic leukemia (CLL) treated with ibrutinib: risk prediction, management, and clinical outcomes

William J Archibald  1 , Kari G Rabe  2 , Brian F Kabat  2 , Joerg Herrmann  3 , Wei Ding  4 , Neil E Kay  4 , Saad S Kenderian  4 , Eli Muchtar  4 , Jose F Leis  5 , Yucai Wang  4 , Asher A Chanan-Khan  6 , Susan M Schwager  2 , Amber B Koehler  4 , Amie L Fonder  4 , Susan L Slager  2 , Tait D Shanafelt  7 , Timothy G Call  4 , Sameer A Parikh  4
Affiliations

Atrial fibrillation in patients with chronic lymphocytic leukemia (CLL) treated with ibrutinib: risk prediction, management, and clinical outcomes

William J Archibald et al. Ann Hematol. 2021 Jan.

Abstract

Background: Ibrutinib therapy is associated with an increased risk of atrial fibrillation (AF) in chronic lymphocytic leukemia (CLL). Risk assessment tools and outcomes of AF in these patients are not well described.

Methods: We performed a retrospective review of patients with CLL treated with ibrutinib at Mayo Clinic between October 2012 and November 2018.

Results: Two hundred ninety-eight patients were identified with a median time on ibrutinib of 19 months (range 0.23-69.7 months). Fifty-one patients developed treatment-emergent AF; the risk of treatment-emergent AF at 6 months, 1 year, and 2 years was 9%, 12%, and 16%, respectively. The following were associated with an increased risk of treatment-emergent AF on multivariable analyses: past history of AF (hazard ratio [HR] 3.5, p = 0.0072) and heart failure (HR 3.4, p = 0.0028). Most patients are able to continue ibrutinib therapy (dose reduced in 43%). Development of treatment-emergent AF was associated with shorter event-free survival (EFS; HR 2.0, p = 0.02) and shorter overall survival (OS; HR 3.2, p = 0.001), after adjusting for age, prior treatment status, TP53 disruption, heart failure, valvular disease, and past history of AF.

Conclusions: Patient comorbidities, rather than CLL-related factors, predict risk of treatment-emergent AF in patients treated with ibrutinib. Although the vast majority of patients with treatment-emergent AF are able to continue ibrutinib (with dose reduction in 43%), treatment-emergent AF appears to be associated with worse outcomes, independent of other adverse prognostic factors.

Keywords: Atrial fibrillation; Chronic lymphocytic leukemia; Ibrutinib; Small lymphocytic lymphoma.

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Figures

Fig. 1
Fig. 1
Cumulative incidence of treatment-emergent atrial fibrillation
Fig. 2
Fig. 2
a Time to atrial fibrillation Framingham risk score. b Time to atrial fibrillation Mayo CLL AF risk score. c Time to atrial fibrillation Italian AF risk score
Fig. 3
Fig. 3
Treatment-emergent atrial fibrillation *Labetalol, metoprolol, carvedilol, atenolol ^digoxin #AV node ablation (n=3); cardioversion (n=11); permanent pacemaker (n=2)
Fig. 4
Fig. 4
Stroke prevention in patients with treatment-emergent AF Anticoagulation agents: apixaban n=15 (29%), rivaroxaban n=5 (10%), enoxaparin n=3 (6%), dabigatran n=1 (2%), warfarin n=1 (2%) Antiplatelet agents: aspirin 81 mg n=9 (18%), aspirin 325 mg n=2 (4%), dual antiplatelet therapy n=1 (2%)
See this image and copyright information in PMC

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