Study Establishes Median PFS, OS Benefits of Ibrutinib in Older Patients With CLL, SLL

The RESONATE-2 study demonstrated that ibrutinib provides significantly longer progression-free survival (PFS), sustained overall survival (OS) benefits, and a high response rate with manageable long-term safety in older patients with previously untreated chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). The results of the study were presented at the Society of Hematologic Oncology 2024 Annual Meeting.

Over a median follow-up period of 10 years, researchers compared single-agent first-line ibrutinib (n = 136) versus 0.5–0.8 mg/kg chlorambucil (n = 133) in patients aged ≥65 years with previously untreated CLL/SLL who did not have del(17p). Patients in the ibrutinib group received 420 mg per day, whereas patients in the chlorambucil group received 0.5–0.8 mg/kg.

The primary endpoints were PFS, OS, overall response rate (ORR), and safety. Patients could cross over to ibrutinib after disease progression on chlorambucil.

The results showed a significant benefit for ibrutinib over chlorambucil. The median PFS was 8.9 years for the ibrutinib group compared with 1.3 years for the chlorambucil group (hazard ratio = 0.16).

After nine years, the PFS rate was 49.7% for ibrutinib-treated patients and 4.4% for patients treated with chlorambucil. Median OS was not reached in the ibrutinib group, with a nine-year OS rate of 68%.

The ORR for ibrutinib was 91%, with a 36% complete response rate. The response rates remained consistent throughout the follow-up period.

Ibrutinib was associated with several side effects, including hypertension (28% and 26% in years eight to nine and nine to ten, respectively) and atrial fibrillation (8% and 9%, respectively). Approximately 25% of patients experienced adverse events (AEs) that led to dose reductions, and 33% discontinued treatment due to AEs. However, 82% of patients who reduced their dose saw their AEs resolve. By the end of the study, 27% of patients remained on ibrutinib, with a median treatment duration of 6.2 years.

In conclusion, the RESONATE-2 study established median PFS and confirmed the sustained OS benefits of continuous first-line single-agent ibrutinib treatment in patients with CLL or SLL, including those with high-risk genomic profiles.

Reference

Burger J, Barr P, Roback T, et al. Final analysis of the RESONATE-2 study: up to 10 years of follow-up of first-line ibrutinib treatment in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma. Abstract #CLL-076. Presented at the Society of Hematologic Oncology 2024 Annual Meeting; September 4-7, 2024; Houston, Texas.