Real-world bleeding risk with ibrutinib

Photo courtesy of Janssen

The Bruton tyrosine kinase inhibitor ibrutinib has been linked to a 20-fold increased risk of major bleeding in blood cancer patients taking concomitant antiplatelet and anticoagulation therapy in a clinical setting.

Caution should be used when weighing the risks and benefits of ibrutinib for patients already taking antiplatelet or anticoagulation therapy, or both, wrote Joseph Mock, MD, of the University of Virginia Health System in Charlottesville, and his colleagues.

Their report was published in Clinical Lymphoma, Myeloma & Leukemia.

Ibrutinib had been associated with an increased risk of bleeding, albeit low, in the clinical trial setting, but the authors suggested this rate could be higher in everyday clinical practice.

“Much of the information [from clinical trials] on the bleeding risk with ibrutinib, included pooled analyses, was from patients exclusively treated in clinical trials with specific exclusion criteria,” the researchers wrote. “These criteria have generally excluded patients with significant comorbidities. However, these patients are seen in clinical practice.”

The researchers conducted a review of patients treated within the University of Virginia Health System between January 2012 and May 2016.

The team identified 70 patients, with an average age of 72, who were taking ibrutinib for chronic lymphocytic leukemia (64%), mantle cell lymphoma (27%), diffuse large B-cell lymphoma (4%), lymphoblastic lymphoma (3%), and Waldenström’s macroglobulinemia (1%).

Bleeding of any grade occurred in 56% of patients, mostly grade 1-2 bruising and epistaxis.

However, major bleeding, defined as grade 3 or higher, occurred in 19% of patients (n=13). Seven of these patients were taking combined antiplatelet and anticoagulant therapy, 4 were taking antiplatelet agents alone, 1 was taking an anticoagulant agent alone, and 1 was taking only ibrutinib.

Univariate analysis showed that the factors associated with an increased risk of major bleeding were antiplatelet or anticoagulant medication, the combination of the 2 medications, interacting medications, anemia (hemoglobin less than 12 g/dL), and an elevated international normalized ratio (INR, > 1.5).

In a multivariate analysis, only the following factors were associated with an increased risk of major bleeding:

• Concomitant antiplatelet and anticoagulant use—hazard ratio=20.0 (95% CI, 2.1-200.0; P=0.0005) vs no antiplatelet/anticoagulant therapy
• Elevated INR—hazard ratio=4.6 (95% CI, 1.1-19.6; P=0.0409).

The researchers said the risk of major bleeding in patients taking both antiplatelet and anticoagulant therapy was “unacceptably high” and “medications other than ibrutinib should be considered” in this patient population.

Overall, the team said their findings confirm “the increasingly recognized risk of major bleeding complications with ibrutinib compared with what was originally reported in the clinical trial setting.”

They noted that this study was limited by the relatively small population size. Their finding that platelet count was not associated with bleeding risk was also “counterintuitive.”

Photo courtesy of Janssen

The Bruton tyrosine kinase inhibitor ibrutinib has been linked to a 20-fold increased risk of major bleeding in blood cancer patients taking concomitant antiplatelet and anticoagulation therapy in a clinical setting.

Caution should be used when weighing the risks and benefits of ibrutinib for patients already taking antiplatelet or anticoagulation therapy, or both, wrote Joseph Mock, MD, of the University of Virginia Health System in Charlottesville, and his colleagues.

Their report was published in Clinical Lymphoma, Myeloma & Leukemia.

Ibrutinib had been associated with an increased risk of bleeding, albeit low, in the clinical trial setting, but the authors suggested this rate could be higher in everyday clinical practice.

“Much of the information [from clinical trials] on the bleeding risk with ibrutinib, included pooled analyses, was from patients exclusively treated in clinical trials with specific exclusion criteria,” the researchers wrote. “These criteria have generally excluded patients with significant comorbidities. However, these patients are seen in clinical practice.”

The researchers conducted a review of patients treated within the University of Virginia Health System between January 2012 and May 2016.

The team identified 70 patients, with an average age of 72, who were taking ibrutinib for chronic lymphocytic leukemia (64%), mantle cell lymphoma (27%), diffuse large B-cell lymphoma (4%), lymphoblastic lymphoma (3%), and Waldenström’s macroglobulinemia (1%).

Bleeding of any grade occurred in 56% of patients, mostly grade 1-2 bruising and epistaxis.

However, major bleeding, defined as grade 3 or higher, occurred in 19% of patients (n=13). Seven of these patients were taking combined antiplatelet and anticoagulant therapy, 4 were taking antiplatelet agents alone, 1 was taking an anticoagulant agent alone, and 1 was taking only ibrutinib.

Univariate analysis showed that the factors associated with an increased risk of major bleeding were antiplatelet or anticoagulant medication, the combination of the 2 medications, interacting medications, anemia (hemoglobin less than 12 g/dL), and an elevated international normalized ratio (INR, > 1.5).

In a multivariate analysis, only the following factors were associated with an increased risk of major bleeding:

• Concomitant antiplatelet and anticoagulant use—hazard ratio=20.0 (95% CI, 2.1-200.0; P=0.0005) vs no antiplatelet/anticoagulant therapy
• Elevated INR—hazard ratio=4.6 (95% CI, 1.1-19.6; P=0.0409).

The researchers said the risk of major bleeding in patients taking both antiplatelet and anticoagulant therapy was “unacceptably high” and “medications other than ibrutinib should be considered” in this patient population.

Overall, the team said their findings confirm “the increasingly recognized risk of major bleeding complications with ibrutinib compared with what was originally reported in the clinical trial setting.”

They noted that this study was limited by the relatively small population size. Their finding that platelet count was not associated with bleeding risk was also “counterintuitive.”

Photo courtesy of Janssen

The Bruton tyrosine kinase inhibitor ibrutinib has been linked to a 20-fold increased risk of major bleeding in blood cancer patients taking concomitant antiplatelet and anticoagulation therapy in a clinical setting.

Caution should be used when weighing the risks and benefits of ibrutinib for patients already taking antiplatelet or anticoagulation therapy, or both, wrote Joseph Mock, MD, of the University of Virginia Health System in Charlottesville, and his colleagues.

Their report was published in Clinical Lymphoma, Myeloma & Leukemia.

Ibrutinib had been associated with an increased risk of bleeding, albeit low, in the clinical trial setting, but the authors suggested this rate could be higher in everyday clinical practice.

“Much of the information [from clinical trials] on the bleeding risk with ibrutinib, included pooled analyses, was from patients exclusively treated in clinical trials with specific exclusion criteria,” the researchers wrote. “These criteria have generally excluded patients with significant comorbidities. However, these patients are seen in clinical practice.”

The researchers conducted a review of patients treated within the University of Virginia Health System between January 2012 and May 2016.

The team identified 70 patients, with an average age of 72, who were taking ibrutinib for chronic lymphocytic leukemia (64%), mantle cell lymphoma (27%), diffuse large B-cell lymphoma (4%), lymphoblastic lymphoma (3%), and Waldenström’s macroglobulinemia (1%).

Bleeding of any grade occurred in 56% of patients, mostly grade 1-2 bruising and epistaxis.

However, major bleeding, defined as grade 3 or higher, occurred in 19% of patients (n=13). Seven of these patients were taking combined antiplatelet and anticoagulant therapy, 4 were taking antiplatelet agents alone, 1 was taking an anticoagulant agent alone, and 1 was taking only ibrutinib.

Univariate analysis showed that the factors associated with an increased risk of major bleeding were antiplatelet or anticoagulant medication, the combination of the 2 medications, interacting medications, anemia (hemoglobin less than 12 g/dL), and an elevated international normalized ratio (INR, > 1.5).

In a multivariate analysis, only the following factors were associated with an increased risk of major bleeding:

• Concomitant antiplatelet and anticoagulant use—hazard ratio=20.0 (95% CI, 2.1-200.0; P=0.0005) vs no antiplatelet/anticoagulant therapy
• Elevated INR—hazard ratio=4.6 (95% CI, 1.1-19.6; P=0.0409).

The researchers said the risk of major bleeding in patients taking both antiplatelet and anticoagulant therapy was “unacceptably high” and “medications other than ibrutinib should be considered” in this patient population.

Overall, the team said their findings confirm “the increasingly recognized risk of major bleeding complications with ibrutinib compared with what was originally reported in the clinical trial setting.”

They noted that this study was limited by the relatively small population size. Their finding that platelet count was not associated with bleeding risk was also “counterintuitive.”