Increased AFib, Major Bleeding with Ibrutinib for Hematologic Malignancies

A new study from the American Society of Hematology (ASH) 2019 annual meeting is adding to the growing amount of evidence that the blood cancer medication ibrutinib could dramatically increase a patient’s risk of atrial fibrillation and other adverse events.

A meta-analysis of close to 4000 patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), mantle-cell lymphoma, Waldenstrom’s macroglobulinemia and diffuse large b-cell lymphoma revealed patients receiving ibrutinib had a 5.37 times greater risk of atrial fibrillation and a 1.73 times greater risk of major bleeding.

In an effort to further detail the potential risk profile associated with ibrutinib, a team of investigators led by Sriman Swarup, MD, MBBS, of Texas Tech University Health Center, conducted an analysis of literature using the MEDLINE and EMBASE databases from inception until June 2019. For the purpose of their analyses, investigators examined phase 3 randomized clinical trials examining ibrutinib in patients with hematological that included the terms atrial fibrillation and major bleeding.

A total of 3920 patients from 10 trials were included in the analysis. Trials included examined ibrutinib in combination and monotherapy compared against more than a half dozen other combination and monotherapies.

Upon analysis, investigators found the atrial fibrillation incidence was 142 (6.52%) in the study group compared to 17 (0.97%) in the control group. Investigators calculated the risk ratio of atrial fibrillation to be 5.37 (95% CI: 2.74-10.54; P<0.0001) with a risk difference to be 0.06 (95% CI: 0.04-0.08; P<0.0001).

In regard to major bleeding, 50 (2.29%) events were observed in the ibrutinib group compared to 21 (1.20%) in the control arm. Based on these results, investigators determined patients in the ibrutinib group were at 1.73-fold (95% CI: 1.03-2.91; P=0.04) increased risk of suffering such an event.

In a subgroup analysis evaluating rates in patients with CLL/SLL, the observed rate of atrial fibrillation was 6.29% higher in the ibrutinib group than in the control arm (RR, 6.14; 95% CI: 2.49-15.14; P<0.0001). Additionally, the rate of major bleeding was 1.32% higher among patients receiving ibrutinib (RR, 2.16; 95% CI: 1.02-4.55; P=0.04).

Within their conclusion, investigators noted the results were concordant with findings of previous research and suggest the use of caution when using ibrutinib in patients who are predisposed to these conditions.

Data from this presentation adds to the apparent risk profile associated with the use of ibrutinib. In a study examining hypertension and incident cardiovascular events in patients receiving ibrutinib for lymphoid malignancies, investigators from the Ohio State Wexner Medical Center found ibrutinib use was associated with new or worsened hypertension in78% of patients within 6 months of beginning treatment.

This study, titled “Updated Meta-Analysis to Evaluate the Incidence of Atrial Fibrillation and Major Bleeding in Patients with Hematologic Malignancies Treated with Ibrutinib,” was presented at ASH 2019.