
Ibrutinib Benefits R/R CLL, but Combo Therapy Works Better
Key Takeaways
- Ibrutinib, a BTK inhibitor, is effective in treating relapsed CLL, with combination therapies improving response rates.
- Combination therapy with ibrutinib and venetoclax, guided by MRD, enhances progression-free survival and allows early treatment discontinuation.
Ibrutinib remains a key treatment for relapsed chronic lymphocytic leukemia (CLL), but findings suggest that combining it with other therapies can improve response rates and may allow for treatment discontinuation in some patients.
Ibrutinib remains a key treatment for relapsed or refractory (R/R)
A meta-analysis published in
Researchers found that single-agent ibrutinib achieved a complete response (CR) rate of 9% and an overall response rate (ORR) of 77%, but the combination therapy yielded even better outcomes. When used with other agents, ibrutinib improved the CR rate to 21% and the ORR to 84%, demonstrating the benefits of multiagent approaches in treating relapsed CLL.
The researchers also observed that adverse events did not significantly impact treatment success. However, toxicity did lead to treatment modifications in some cases, with 16% to 24% of patients discontinuing ibrutinib due to intolerance and 13% to 23% requiring dose adjustments.
“Evaluating ibrutinib’s adverse effects revealed varying trends in grade 3 and 4 events while highlighting consistent neutropenia, anemia, and thrombocytopenia patterns,” the authors wrote. “Nevertheless, the differences in results and the heterogeneity in comparisons with other medications or combinations emphasize the need for additional research to improve treatment methods for patients with R/R CLL, focusing on both effectiveness and adverse effects.”
Ibrutinib’s Role in CLL Treatment
CLL is a slow-growing B-cell malignancy that primarily affects older adults.2 Although chemoimmunotherapy has been a traditional treatment, many patients exhibit resistance or are ineligible due to age and comorbidities.1 Ibrutinib, a Bruton tyrosine kinase (BTK) inhibitor, has emerged as a targeted therapy that disrupts malignant B-cell proliferation.
Other researchers are also looking into how to combine ibrutinib with other treatments to boost outcomes.
Although the combination of ibrutinib and venetoclax showed strong efficacy, the FLAIR trial also highlighted the need for careful management of adverse events, particularly cardiac complications. These findings align with the meta-analysis' conclusion that combination therapy enhances treatment responses, reinforcing the importance of ongoing research into multiagent regimens and personalized treatment approaches for CLL.
More Research Needed
The meta-analysis had notable limitations.1 According to the authors, the substantial heterogeneity among the 21 included studies made direct comparisons challenging, as there were variations in treatment regimens and combination therapies. Additionally, incomplete reporting of survival outcomes restricted the assessment of long-term efficacy, with only progression-free and overall survival metrics available in several cases.
“Future research is recommended to validate these findings and strengthen the results by achieving greater statistical robustness,” the authors said.
References
1. Karimi MA, Norooziseyedhosseini H, Khademi R, et al. Real world results of ibrutinib in patients with relapsed or refractory chronic lymphocytic leukemia: a meta-analysis of clinical studies. BMC Pharmacol Toxicol. 2025;26(1):43. doi:10.1186/s40360-024-00832-9
2. Chronic lymphocytic leukemia. Mayo Clinic. Updated December 20, 2024. Accessed March 4, 2025.
3. Klein HE. Personalized CLL therapy with MRD guidance improves survival outcomes. AJMC®. February 6, 2025. Accessed March 4, 2025.
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