# Comparison of One-Year Adverse Events Between First- and Second-Generation Bruton’s Tyrosine Kinase Inhibitors: A Retrospective Study

## TL;DR

This study compares the side effects of three Bruton’s tyrosine kinase inhibitors in real-world patients over one year.

## Contribution

It provides real-world comparative data on adverse events of first- and second-generation BTK inhibitors.

## Key findings

- All BTKi agents caused bone marrow suppression, infection, and bleeding.
- Cardiac-related adverse events occurred only with ibrutinib.
- Several Grade 3 or higher events were observed, highlighting the need for careful monitoring.

## Abstract

Background/Aim: Bruton’s tyrosine kinase inhibitors (BTKi) are important targeted agents for hematological malignancies. Second-generation BTKi are considered to have fewer off-target enzyme effects than first-generation agents; however, real-world comparative data on adverse events (AEs) remain limited. AEs of special interest with BTKi include bone marrow suppression, infection, hemorrhage, and cardiac-related events. This study aimed to investigate the frequency and severity of AEs of special interest associated with the three BTKi, namely, ibrutinib (IBR), tirabrutinib (TIR), and acalabrutinib (ACB), in real-world clinical practice.

Methods: We retrospectively investigated cytopenia and non-hematologic toxicities, including infections, bleeding, and cardiovascular AEs, for up to one year in patients who received BTKi at Fujita Health University Hospital and an affiliated hospital between March 2016 and March 2025 (IBR, n = 24; TIR, n = 24; ACB, n = 5). Data were collected from electronic medical records and graded according to the Common Terminology Criteria for Adverse Events, version 5.0.

Results: In the IBR group, the median age was 76 years (range, 76-81 years). Cytopenia, infections, bleeding, and cardiovascular AEs occurred in 21 (87.5%), nine (37.5%), eight (33.3%), and four (16.6%) patients, respectively. In the TIR group, the median age was 70 years (range, 64-76 years). Cytopenia, infections, and bleeding occurred in 17 (70.8%), seven (29.1%), and six (25.0%) patients, respectively. In the ACB group, the median age was 68 years (range, 52-75 years), and cytopenia was observed in four (80.0%) patients.

Conclusion: All BTKi agents were associated with bone marrow suppression, infection, and bleeding, whereas cardiac-related AEs occurred only with IBR. Several Grade 3 or higher events were identified, underscoring the need for careful monitoring of patients receiving BTKi in clinical practice.