Increased Atrial Fibrillation/Stroke Risk Did Not Impact TTD/TTNT Outcomes Associated with Ibrutinib for CLL/SLL

Outcomes such as time to discontinuation and time to next treatment were not impacted by a high risk of atrial fibrillation or stroke at baseline in patients receiving ibrutinib (Imbruvica) for chronic lymphocytic leukemia or small cell lymphocytic lymphoma, according to data from a real-world study published in Clinical Lymphoma, Myeloma, and Leukemia.

In first-line treatment, the median real-world time to discontinuation (TTD) was 15.7 months for all patients, 11.7 months for patients at high risk for atrial fibrillation, and 13.7 months for patients at high risk for stroke. In the second-line and later, the median TTD was 12.5 months for the overall cohort, 9.5 months for the CHARGE-AF cohort, and 10.6 months for the CHA₂DS₂-VASc cohort. The median time to the next treatment (TTNT) was longer for patients receiving ibrutinib vs other regimens, with the median not being reached in the first-line vs 45.0 months. In the second-line and beyond, the median TTNT was not reached vs 23.6 months with ibrutinib and other regimens, respectively. The median TTNT was 45.9 months in the first-line setting vs 23.6 months in the second-line setting (P <.05). The TTNT was not reached for the CHA₂DS₂-VASc and CHARGE-AF high-risk patients receiving ibrutinib in the first and second line and later, it was not reached in the first-line for other regimens, but was 24.3 months in the second line and beyond (P <.05).

Electronic medical records in the Flatiron Health database were analyzed, with 7585 patients meeting the inclusion criteria for the study. A total of 2190 patients received ibrutinib in the firstline vs 1851 in second line. Based on CHARGE-AF risk score, 20% of patients in the ibrutinib cohort in the first-line and 17.5% in the second line and later were at a higher risk of atrial fibrillation. Of those receiving other regimens, a high risk of atrial fibrillation was observed in 15.6% of patients in the first line vs 20.8% in the second line and later. A total of 49.3% of patients receiving ibrutinib had a high-risk CHA₂DS₂-VASc score and were at a high risk of stroke in the first line vs 44.5% in the second line. Among those receiving other regimens, the CHA₂DS₂ -VASc risk score was high in 44.3% of patients in the first-line setting vs 50.5% in the second-line setting.

For patients receiving first-line ibrutinib, the median follow-up was 23.1 months in all patients, 19.5 months in the CHARGE-AF high-risk patients, and 21.3 months in the CHA₂ DS₂ -VASc high-risk patients compared with 22.1 months, 18.0 months, and 19.8 months in the second-line setting or later, respectively. For those receiving other regimens, the median follow-up was 33.0 months in all patients, 25.6 months in the CHARGE-AF group, and 28.0 months in CHA₂DS₂ -VASc group, compared with 16.7 months, 12.4 months, and 14.7 months in the second-line setting, respectively.

In the first-line setting, the median age was 72 years in the ibrutinib cohort vs 71 years in the other regimen cohort. Those treated with ibrutinib had a higher incidence of 17p deletion with 24.2% in the first line vs 25.5% in the second line compared with other regimens at 7.5% vs 11.2%, respectively. Common comorbidities across cohorts included hypertension and diabetes.

A total of 1.9% of patients experienced atrial fibrillation at baseline in the ibrutinib cohort in the first-line setting vs 1.8% in the other regimens compared, and 1.9% vs 3.0% in the second-line setting, respectively. Atrial flutter was observed in 0.1% during the baseline period in the first-line setting vs 3.0% in the second-line setting and beyond. Patients had similar Atherosclerotic Cardiovascular Disease Scores across lines of treatment and regimens including 18.9% with first-line ibrutinib vs 17.2% for other regimens compared, and 17.5% vs 19.5% in the second line and later, respectively.

Reference

Narezkina A, Akhter N, Lu X, et al. Real-world persistence and time to next treatment with ibrutinib in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma including patients at high risk for atrial fibrillation or stroke. Clin Lym Myeloma Leuk. Published online July 15, 2022. doi:10.1016/j.clml.2022.07.004