With follow-up of up to eight years, the long-term results of the RESONATE-2 trial demonstrate sustained progression-free and overall survival with the use of first-line ibrutinib for chronic lymphocytic leukemia (CLL).
“The breadth of experience with targeted agents is still expanding; however, ibrutinib has the longest demonstrated efficacy across multiple phase 3 studies, whereas other targeted agents, including follow-on BTK inhibitors, approved or in development for CLL, lack comparable long-term data,” wrote researcher Paul Barr, MD, of the Wilmot Cancer Institute, University of Rochester Medical Center, and colleagues. “Here, we demonstrated, in the longest follow-up to date from a phase 3 study of first-line novel agent therapy in patients with CLL/SLL, that nearly half of patients with CLL/SLL were able to receive long-term continuous first-line treatment with single-agent ibrutinib.”
RESONATE-2 is a phase 3, multicenter, international trial comparing the efficacy and safety of ibrutinib versus chlorambucil in first-line CLL/small lymphocytic lymphoma (SLL). Previously untreated patients aged 65 or older and without chromosome 17p deletion were randomly assigned to ibrutinib or chlorambucil until disease progression or unacceptable toxicity.
Primary results from the study showed superior efficacy and tolerability of ibrutinib; the drug received FDA approval for patients with CLL/SLL in the first-line setting based on data from the trial.
“Evidence from RESONATE-2 also showed that patients with high-risk genomic features, such as chromosome 11q deletion (del[11q]) or unmutated immunoglobulin heavy chain variable region (IGHV) that predict inferior outcomes with chemotherapy and chemoimmunotherapy, experienced significantly improved long-term efficacy outcomes with single-agent ibrutinib versus chlorambucil,” the researchers wrote.
With up to eight years follow-up, the median progression-free survival has not yet been reached for patients assigned to ibrutinib compared with 15 months for chlorambucil. Ibrutinib led to an 85% reduction in the risk of progressive disease or death (hazard ratio=0.154). A sustained benefit of ibrutinib was maintained across subgroup analyses including advanced stage and bulky disease, and in those with high-risk genomic features.
Median overall survival has not been reached for patients assigned to ibrutinib; the 7-year survival estimate was 78%.
Overall response rate was 92% for patients assigned ibrutinib compared with 37% for patients assigned to chlorambucil.
No new safety signals emerged.
“These unprecedented long-term data among phase 3 studies of a targeted agent in the first-line treatment of patients with CLL/SLL provide important data for informed decision-making in the current treatment landscape,” the researchers wrote.
Barr PM, Own W, Robak T, et al. Up to 8 Years Follow-up From RESONATE-2: First-Line Ibrutinib Treatment for Patients With Chronic Lymphocytic Leukemia. Blood Adv. 2022 Apr 4;doi: 10.1182/bloodadvances.2021006434