Can Reducing Dosage Manage Cardiac Toxicities in Ibrutinib?

Bruton’s tyrosine kinase inhibitors carry risks for adverse cardiac events. In the case of ibrutinib, adverse events (AEs) are more common in the first year of treatment. Researchers, led by Alessandra Tedeschi, MD, investigated whether dose reductions of ibrutinib after early AEs could limit safety risks while allowing patients with CLL to continue treatment with ibrutinib and venetoclax.

Based on a pooled analysis of 1210 clinical trial participants, the investigators suggested that dose reductions of ibrutinib after early cardiac AEs did not impact progression-free survival or overall survival, and AE rates were lower among patients who had a dose reduction compared with those who did not. Findings were presented at the 17th International Conference on Malignant Lymphoma.

Ibrutinib Can Be used Safely After Cardiac AEs

The analysis reviewed cardiac AEs in the 12 months after treatment initiation from 3 clinical trials on continuous ibrutinib monotherapy (n=379), 2 on continuous ibrutinib-based combination therapy (n=402), and 2 on time-limited ibrutinib with venetoclax (n=429).

Notably, 212 patients had a cardiac AE, with 72 being grade 3 or 4. Of these AEs, 52 (25%) occurred in ibrutinib monotherapy patients, 75 (35%) in ibrutinib plus anti-CD20 monoclonal antibody patients, and 85 (40%) in ibrutinib plus venetoclax patients.

Overall, 17 (8%) patients had a dose reduction of ibrutinib, though only 4 of those were following a cardiac AE. Specifically, dose reductions occurred in 3 (18) monotherapy patients, 5 (29%) ibrutinib plus anti-CD20 patients, and 9 (53%) ibrutinib plus venetoclax patients. Authors noted that 8 (89%) of the 9 ibrutinib plus venetoclax patients went on to complete treatment.

The median follow-up was 21.8 months for patients with dose reductions compared with 16.0 months for patients without. Authors highlighted that no patient with a dose reduction had a serious or overall cardiac AE that recurred at the same or worse severity, whereas patients without reductions had recurrence rates of 22% and 11%, respectively.

The authors closed their poster with the suggestion that active management of cardiac AEs via ibrutinib dose reductions may allow patients with CLL or SLL to continue treatment “while mitigating risks for recurrence or worsening of cardiac AEs.”

More from ICML: Venetoclax Regimens Show Promise for CLL With Richter’s Transformation