Dr Shadman on the Impact of Early Dose Reduction on Real-World Outcomes With Ibrutinib in CLL/SLL

Mazyar Shadman, MD, MPH, Innovators Network Endowed Chair, associate professor, Clinical Research Division, Fred Hutchinson Cancer Center; associate professor, Medical Oncology Division, University of Washington School of Medicine, discusses real-world outcomes following early dose adjustments of first-line ibrutinib (Imbruvica) in Medicare beneficiaries with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL).

The first-in-class covalent BTK inhibitor ibrutinib is currently approved by the FDA for use in both the frontline and relapsed settings for patients with CLL, Shadman begins. However, adverse effects (AEs) and subsequent treatment discontinuations have been significant issues associated with ibrutinib use, he says. Despite these challenges, ibrutinib offers flexibility in terms of dose adjustments and reductions, which can be pivotal in managing these AEs, Shadman notes. Previous studies have shown that early dose adjustments can help patients remain on ibrutinib longer, thereby improving efficacy and extending the time to the next treatment, he adds.

At the 2024 ASCO Annual Meeting, Shadman and colleagues presented findings from a study evaluating whether early dose reductions following AEs could enable patients to remain on ibrutinib longer. Using claims data from Medicare beneficiaries, researchers identified patients with CLL who started ibrutinib as first-line therapy. Patients were divided into 2 cohorts: those who underwent dose reduction after their first AE and those who did not.

The results indicated that patients who had an early dose reduction following their first AE stayed on treatment longer and had a longer time to the next treatment, Shadman reports, noting that this metric is often used as a proxy for progression-free survival. Additionally, analysis of the claims data revealed that early dose reductions were associated with lower health-related costs, including overall CLL-related costs and health resource utilization, he says. These findings suggest that early dose adjustment of ibrutinib following the onset of AEs can be a crucial strategy in managing patients with CLL. By adjusting the dose early, patients are more likely to remain on therapy, continue to benefit from its efficacy, and avoid the need for more intensive subsequent treatments, Shadman explains. This study underscores the importance of personalized treatment management to optimize outcomes for patients receiving ibrutinib treatment, he concludes.