TY - JOUR
T1 - Atrial fibrillation in patients with chronic lymphocytic leukemia (CLL) treated with ibrutinib
T2 - risk prediction, management, and clinical outcomes
AU - Archibald, William J.
AU - Rabe, Kari G.
AU - Kabat, Brian F.
AU - Herrmann, Joerg
AU - Ding, Wei
AU - Kay, Neil E.
AU - Kenderian, Saad S.
AU - Muchtar, Eli
AU - Leis, Jose F.
AU - Wang, Yucai
AU - Chanan-Khan, Asher A.
AU - Schwager, Susan M.
AU - Koehler, Amber B.
AU - Fonder, Amie L.
AU - Slager, Susan L.
AU - Shanafelt, Tait D.
AU - Call, Timothy G.
AU - Parikh, Sameer A.
N1 - Funding Information:
The authors would like to thank the participating patients treated at Mayo Clinic. The results of this study were presented as a poster at the Annual American Society of Clinical Oncology Meeting in Chicago, IL, in June 2019. The conduct of this research was supported in part by the Henry J Predolin Foundation. Sameer A. Parikh also acknowledges support from the Mayo Clinic K2R Career Development Program.
PY - 2021/1
Y1 - 2021/1
N2 - 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.
AB - 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.
KW - Atrial fibrillation
KW - Chronic lymphocytic leukemia
KW - Ibrutinib
KW - Small lymphocytic lymphoma
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U2 - 10.1007/s00277-020-04094-3
DO - 10.1007/s00277-020-04094-3
M3 - Article
C2 - 32488603
AN - SCOPUS:85085881576
VL - 100
SP - 143
EP - 155
JO - Annals of Hematology
JF - Annals of Hematology
SN - 0939-5555
IS - 1
ER -