Real-world Outcomes of Ibrutinib Dose Reduction Versus No Reduction After AEs

By Patrick Daly - Last Updated: September 14, 2023

Trials on first-line ibrutinib monotherapy in treatment-naïve patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma have reported that patients who had an ibrutinib dose reduction due to adverse events (AEs) had efficacy outcomes similar to those who did not have a reduction.

However, researchers stated that current real-world data on ibrutinib dosing patterns and related outcomes are sparse. Investigators reviewed a US insurance claims database to identify real-world dosing patterns and time to next treatment (TTNT) in patients with a dose reduction versus those without. Their study was featured at the 2023 Society of Hematologic Oncology Annual Meeting.

According to the study’s lead author, Mazyar Shadman, MD, patients with a dose reduction due to an AE actually had a longer TTNT compared with those who did not have a dose reduction. The authors did note their analysis could not establish causal associations between specific AEs and subsequent dose reductions.

Ibrutinib Dose Reduction Improves Treatment Patterns in CLL

Starting from February 2014, the analysis identified 658 patients treated with first-line single-agent ibrutinib 420 mg who had an AE during treatment and at least 90 days of follow-up after initiating treatment. Patients who discontinued ibrutinib were included in both groups. Time-varying Cox proportional hazards models were used to evaluate TTNT, defined as time from AE to first dose of another treatment or death.

After a recorded AE, 95 (14%) patients had an ibrutinib dose reduction and 563 (86%) did not. The study’s authors identified the following treatment patterns for patients with or without a dose reduction:

With dose reduction Without dose reduction
Mean ibrutinib treatment duration 922 days (median, 842) 735 days (median, 606)
Mean time to first AE 161 days (median, 51) 227 days (median, 119)
Mean time from AE to end of therapy 760 days (median, 725) 508 days (median, 352)


Next treatment or death was less common in patients with a dose reduction (31%) versus patients without (39%), and the median TTNT was 59.5 months versus 30.6 months, respectively (unadjusted hazard ratio [HR], 0.56; P=.003; adjusted HR, 0.62; P=.017). Authors stated that patterns were similar between cardiac and noncardiac AE subgroups.

“Using TTNT as a marker for disease progression,” the report concluded, “these findings suggest that ibrutinib dose reduction can be an effective strategy to manage adverse events while delaying disease progression.”

Related: Venetoclax Efficacy in Patients With CLL Who Relapsed After HSCT

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