ASCO 2024: Reducing Ibrutinib Dose Impacts Time to Next CLL Treatment

CLL specialist Dr. Mazyar Shadman from Fred Hutchinson Cancer Center in Seattle, Washington, shared his findings at the ASCO 2024 conference in June about how decreasing the dose of ibrutinib for CLL patients who experienced side effects extended the amount of time until they needed their next CLL treatment. Read a summary of the key findings below. 

What is Ibrutinib? 

Ibrutinib (Imbruvica, Janssen Biotech) is the first FDA-approved Bruton's tyrosine kinase (BTK) inhibitor for CLL. It stops CLL progression by silencing the BTK protein, a molecule that aids the growth and maturation of B-cells. Click here to learn more about BTK inhibitors for CLL. 

Ibrutinib is a pill taken indefinitely until patients can’t tolerate treatment or CLL cells become resistant, leading to a relapse. To help patients reduce ibrutinib-related side effects, CLL specialists often suggest reducing the medicine’s dose. This can aid patients in remaining on ibrutinib, keeping the CLL at bay. 

Common side effects of ibrutinib include decreased blood counts, diarrhea, bruising, infections, and fatigue. Second-generation BTK inhibitors like acalabrutinib (Calquence, AstraZeneca) and zanubrutinib (Brukinsa, BeiGene) are often recommended over ibrutinib as they have fewer side effects. 

Dr. Shadman and colleagues wanted to evaluate if reducing the ibrutinib dose for patients who experienced a side effect impacted the amount of time in between needing to start their next CLL treatment compared to those who continued at full dose. 

Evaluating the time until the next CLL treatment indicates how long the first therapy prevented the progression of CLL.

Does Reducing Ibrutinib Dose Impact Time to Next CLL Treatment? 

For CLL patients who experienced a side effect from ibrutinib, the amount of time until they needed a different CLL therapy was: 

• 50 months for patients who did receive an ibrutinib dose reduction 
• 22 months for patients who did not receive an ibrutinib dose reduction 

The study also found that other factors increased the risk of patients needing to discontinue ibrutinib treatment. These included older age, comorbidities (additional health conditions apart from CLL), healthcare costs, and hospitalizations. Another interesting finding is that fewer patients in the dose-reduction group discontinued the treatment. 

In conclusion, among CLL patients who experienced a side effect after starting ibrutinib as their first treatment, patients who received a dose reduction of ibrutinib had a significantly longer time between needing to begin their next CLL therapy than those who did not. This shows that reducing the dose of ibrutinib may be a safe and effective strategy for managing side effects while maintaining control of CLL.

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Source

• Real-world outcomes following adverse events and dose reduction of first-line ibrutinib in Medicare beneficiaries with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL).