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Risk score predicts atrial fibrillation with ibrutinib therapy for chronic lymphocytic leukemia

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William J. Archibald

CHICAGO — The Italian risk score accurately predicted risk for atrial fibrillation among patients treated with ibrutinib for chronic lymphocytic leukemia, according to data from a retrospective review presented at ASCO Annual Meeting.

“Ibrutinib [Imbruvica; Pharmacyclics] causes an increased risk for bleeding and an increased risk for atrial fibrillation; thus, treating clinicians are in a difficult position,” William J. Archibald, MD, resident physician at Mayo Clinic in Rochester, Minnesota, told HemOnc Today. “On one hand, CLL can be very well-controlled with ibrutinib therapy with minimal side effects, but if a patient develops atrial fibrillation, combining ibrutinib and anticoagulation could cause an unacceptably high risk for bleeding. If we have to stop ibrutinib therapy because atrial fibrillation develops, other therapies for CLL may not be as well-tolerated and the CLL may not respond to other therapies. By being able to predict which patients are more likely to develop atrial fibrillation with information that clinicians already have on hand, the treating clinician can make different treatment decisions.”

Researchers assessed three clinical prediction models — the Framingham, Italian and Shanafelt risk scores — among 298 patients (median age, 67 years; range, 35-93; 70.5% men) with CLL receiving treatment at Mayo Clinic between 2012 and 2018. Patients had a cumulative 565 years of ibrutinib exposure.

After a median follow-up 24 months (range, 0-70), 51 patients developed treatment-emergent atrial fibrillation, of whom 80% had a CHA 2 DS 2 -VASc score — an indicator of stroke risk — of 2 or higher. To prevent stroke, 40% of those patients received anticoagulation alone, 14% received antiplatelet therapy alone and 10% received both.

Most (73%) incidences of atrial fibrillation were grade 2; 25% were grade 3 or worse.

Investigators found that the Italian risk score — which uses Akaike information criteria — was the best predictor for treatment-emergent atrial fibrillation. The 2-year risk for atrial fibrillation with score 0 was 6%, followed by 8% with score 1 to 2, 26% with score 3 to 4, and 47% with score 5 or higher.

Overall, 61% of patients received medical therapy for atrial fibrillation and 31% of patients underwent interventional therapy.

Among those with atrial fibrillation, 12% permanently discontinued ibrutinib, 23% temporarily discontinued ibrutinib and later resumed the original dose, 43% continued on a reduced-dose regimen, and 22% continued the initial dose.

Investigators observed shorter EFS (HR = 2.5; 95% CI, 1.5-4.2) and shorter OS (HR = 3.5; 95% CI, 2-6.3) among patients who developed atrial fibrillation.

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Two major bleeds occurred, including one in a patient receiving concomitant antiplatelet and anticoagulation therapy, and one in a patient receiving neither.

No patient with treatment-emergent atrial fibrillation experienced thrombotic stroke.

“We are hoping to look at this issue prospectively and expand on other groups’ work for having patients evaluated with echocardiography or electrocardiography prior to beginning ibrutinib therapy to see if there is any benefit in more aggressively screening patients for atrial fibrillation risk factors — especially in patients with a high score on the Italian risk model prior to beginning therapy,” Archibald said. “We are encouraged that ibrutinib can be continued through the development of atrial fibrillation and the use of anticoagulation without a significant adverse toxicity profile.” – by Jennifer Southall

Reference:

Archibald WJ, et al. Abstract 7522. Presented at: ASCO Annual Meeting; May 31-June 4, 2019; Chicago.

Disclosures: Archibald reports no relevant financial disclosures. Please see the abstract for all other authors’ relevant financial disclosures.