Ibrutinib Dose Adjustments Do Not Impact Time to Next Treatment For Patients With Chronic Lymphocytic Leukemia

For patients with chronic lymphocytic leukemia (CLL), a flexible dosing approach with first-line ibrutinib yielded similar time to next treatment (TTNT) compared with those who sustained their dosages. The results of this study were presented at the 65th ASH Annual Meeting & Exposition in San Diego, California.

Ibrutinib is a once-daily Bruton’s tyrosine kinase inhibitor (BTKi) that is generally recommended as the first-line treatment for patients with CLL. Although dosing flexibility allows patients to prevent or reduce adverse events, the researchers aimed to determine whether such adjustments impact patients’ TTNT, defined as the time from the index date to the initiation of a next treatment.

In a real-world analysis, the researchers utilized a specialty pharmacy electronic medical records database that includes data from academic and non-teaching hospital systems in the United States to identify adults with CLL who initiated first-line, single-agent ibrutinib at a starting dose of 420 mg/day (n = 1171). Next, they compared the TTNT for patients initiating and sustaining first-line ibrutinib at 420 mg/day for at least 12 months vs those having a dose adjustment within 3 months to 12 months. The researchers also conducted sensitivity analyses that captured dose adjustments at different time intervals, including 3 to 6 months, 3 to 9 months, and 3 to 18 months, and they replicated the analysis for patients with CLL at high risk for a cardiovascular (CV) event (n = 724) based on pre-existing CV conditions or a high CV risk score.

Among the involved patients, the mean age was 70.4 years and 34.6% were female. Additionally, a total of 61.8% were classified as high risk for a CV event. The mean follow-up was 29.8 months.

A total of 229 patients (19.6%) had a dose adjustment (DA) at any time. Of these, 178 (77.7%) adjusted their dose to 280 mg/day with a mean time to a DA of 9 months. A total of 111 patients (48.5%) had a DA between 3 months to 12 months, 66 (28.8%) between 3 months to 6 months, 87 (38.0%) between 3 months to 9 months, and 126 (55.0%) had a DA between 3 months to 18 months.

A total of 90 (7.7%) patients initiated a next treatment, of which 59 (65.6%) initiated a venetoclax-based regimen as their subsequent therapy.

A pooled logistic regression model indicated that a DA was not associated with an increased risk of having a next treatment (adjusted hazard ratio = 1.14; [95% CI, 0.80 to 1.62]); p = 0.47). Results were also consistent in the subgroup with a high risk for a CV event.

“This large real-world analysis of CLL patients from academic and non-teaching hospital systems showed that undergoing DA of first-line ibrutinib yielded similar clinical outcomes compared to having no DA, with similar findings for the high CV risk subgroup,” the authors concluded. “These findings, along with those from clinical trials and real-world community oncology practices, suggest that a flexible dosing approach with ibrutinib may be an effective approach in allowing patients to achieve optimal outcomes while remaining on long-term continuous first-line treatment.”

Reference:

Ghosh N, Qureshi ZP, Ding Z, et al. Ibrutinib dose adjustment does not impact time to next treatment in first-line patients with chronic lymphocytic leukemia: a real-world analysis of electronic medical records from academic and non-teaching hospitals using target trial emulation. Paper presented at: 65th ASH Annual Meeting & Exposition. San Diego, CA. December 9, 2023. https://ash.confex.com/ash/2023/webprogram/Paper186284.html