December 10, 2023
By Catlin Nalley
Real-world findings suggest that a flexible dosing strategy for ibrutinib may be an effective option for patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) in the first-line setting. These findings were recently presented by study author Nilanjan Ghosh, MD, PhD, Atrium Health Levine Cancer Institute, Charlotte, NC, during the 65th American Society of Hematology (ASH) Annual Meeting and Exposition, held December 9-12 in San Diego (Abstract 270).
“Ibrutinib, a once-daily BTK inhibitor, is recommended as first-line treatment for patients with chronic lymphocytic leukemia/small lymphocytic lymphoma,” Ghosh said. “Dosing flexibility with ibrutinib helps prevent recurrence or worsening of adverse events while maintaining treatment efficacy.
“However, what is lacking is a formal statistical approach mimicking a clinical trial in the real-world setting to compare clinical outcomes between patients with or without ibrutinib dose adjustments,” he continued.
To fill this gap, Ghosh and colleagues initiated the current study comparing the real-world effectiveness in terms of time-to-next treatment of two strategies—dose adjustment and standard dose—in patients with CLL/SLL who were treated with first-line ibrutinib.
The dose adjustment strategy involved single-agent ibrutinib (420 mg/day) for 3 to 12 months, followed by dose adjustment to any dose below 420 mg/day until the initiation of the next treatment or ibrutinib treatment discontinuation. The standard dose strategy, according to Ghosh, was sustained ibrutinib treatment at 420 mg/day for more than 12 months until the initiation of the next treatment or ibrutinib treatment discontinuation.
The overall study population included 3,342 patients and the subgroup analysis—patients with high cardiovascular risk—included 2,640 individuals. Among patients in the overall population, 608 (18%) had a dose adjustment anytime post-index over a median follow-up of 19.6 months. Of these patients, 281 (46%) experienced a dose adjustment between 3 and 12 months post-index.
During the study period, Ghosh reported that 463 patients (14%) initiated a subsequent line of therapy. “The ibrutinib dose adjustment strategy (420 mg/day for 3-12 months followed by a dose adjustment) was not associated with increased risk of initiating next treatment when compared with the standard dose strategy (sustained treatment at 420 mg/day for more than 12 months).”
Examination of subgroups and alternative dose adjustment strategies showed that “ibrutinib dose adjustment strategy was not associated with an increased risk of initiating next treatment when considering alternative durations of treatment with ibrutinib at 420 mg/day prior to dose adjustment (3-6 months or 3-9 months).”
Ghosh also noted that results for the subgroup of patients with high cardiovascular risk were consistent with the overall study cohort.
“In this real-world study with CLL/SLL frontline ibrutinib, a small proportion of patients required a subsequent dose adjustment (18% over a median follow-up duration of 19.6 months),” said Ghosh.
“Ibrutinib dose adjustment within 3-12 months post-index was not associated with an increased risk of initiating next line of treatment when compared with continuous standard dose treatment,” he concluded. “These results suggest that employing a flexible dosing approach with ibrutinib may be an effective management strategy in achieving an optimal balance between clinical therapeutic efficacy and safety for patients with CLL/SLL in the first-line setting.
Catlin Nalley is a contributing writer.