Study Investigates Recurrent Cardiac Events, Outcomes After Ibrutinib Dose Reduction

A pooled analysis of 10 clinical trials found that ibrutinib dose reductions were associated with lower rates of recurrent cardiac adverse events (AEs) in patients with B-cell malignancies. This study was presented as a poster at the Hematology/Oncology Pharmacy Association Annual Conference 2024.

“Dose reduction is a potential AE management approach to optimize ibrutinib treatment outcomes and avoid early discontinuation,” the authors wrote in their poster.

Ten clinical trials were included, with patients treated for chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), mantle cell lymphoma (MCL), marginal zone lymphoma (MZL), or Waldenström macroglobulinemia (WM). The daily starting dose was ibrutinib 420 mg for patients with CLL/SLL and WM and 560 mg for patients with MCL and MZL.

The total pooled population was 1263 patients, of whom 234 experienced a cardiac AE. After exclusion of patients who had a dose reduction prior to cardiac AE or fatal cardiac AE with no prior cardiac AE, 222 patients remained in the analysis. Of this group, 22 patients had an ibrutinib dose reduction and 200 did not.

The recurrence rate of cardiac AEs was lower in the subgroup of patients with a dose reduction. Fourteen percent of patients in the dose-reduction group experienced a grade 1-4 cardiac AE recurrence compared with 19% of the group without a dose reduction. Regarding serious AEs, 5% of the dose-reduction group had a recurrent serious AE compared with 11% of the no-reduction group. No patients in either group died due to recurrence of cardiac AEs.

Dose reductions for cardiac AEs did not impact progression-free survival (PFS) in patients with a starting dose of 420 mg. The median PFS in the dose-reduction group was not reached at the time of data cutoff; in the no-reduction group, the median PFS was 34.8 months. The 24-month PFS rates were 94% and 71% in the dose-reduction and no-reduction groups, respectively. Across the entire cohort, the 24-month PFS rates were 91% and 63% in those who did or did not have a dose reduction, respectively.

Similarly, overall survival (OS) was not negatively impacted by dose reductions in those with a starting dose of 420 mg. The 24-month OS in this subgroup was 94% and 83% in those with or without a dose reduction, respectively. The median OS was not reached in either group at data cut-off.

“Rates of recurrence of same/worse severity or serious cardiac AE were lower among patients who had an ibrutinib dose reduction than in patients without any dose reduction,” the authors summarized. “Oncology pharmacists provide dose reduction recommendations for cardiac AEs, which may enable patients to continue to benefit from long-term ibrutinib and mitigate the risk of AE recurrence or worsening.”

Reference

Stephens D, Brown JR, Ma S, et al. Ibrutinib dose modifications for management of cardiac adverse events in patients with b-cell malignancies: pooled analysis of 10 clinical trials. Poster. Presented at the Hematology/Oncology Pharmacy Association Annual Conference 2024; April 3-6, 2024; Tampa, Florida.