Single-agent ibrutinib given in the first-line setting sustained a progression-free survival and overall survival benefit compared with chlorambucil as therapy for patients with chronic lymphocytic leukemia at 7-year follow-up.
Single-agent ibrutinib (Imbruvica) given in the first-line setting sustained a progression-free survival (PFS) and overall survival (OS) benefit compared with chlorambucil as therapy for patients with chronic lymphocytic leukemia (CLL) at 7-year follow-up, according to data presented virtually during the 2021 ASCO Annual Meeting.1
Further, first-line treatment with ibrutinib in the phase 3 RESONATE-2 study (NCT01722487) reported no new safety signals at the long-term follow-up.
“Overall, in the longest follow-up to date, up to 7 years, from a phase 3 study of first-line [Bruton tyrosine kinase]–directed therapy, single-agent ibrutinib conferred sustained PFS and OS benefit versus chlorambucil,” Paul M. Barr, MD, associate professor of medicine and director of the Clinical Trials Office for the Wilmot Cancer Institute at the University of Rochester Medical Center, said in his presentation of the data.
A total of 269 previously untreated patients with CLL or small lymphocytic lymphoma aged 65 or older were randomly assigned 1:1 to either ibrutinib or chlorambucil. The median follow-up time was 6.2 years (range, 0.06-7.2).
Overall, with up to 7 years of follow-up, the median PFS for patients in the ibrutinib arm was not reached (HR, 0.160; 95% CI. 0.111-0.230), equating to an 84% reduction in the risk of progression or death.
It’s estimated that, at 6.5 years, 61% of patients in the ibrutinib arm and 9% of patients in the chlorambucil arm were progression free and alive.
“Superior benefit for ibrutinib versus chlorambucil was maintained across subgroup analysis factors, including high-risk genomic features and other baseline clinical characteristics such as advanced stage and bulky disease,” explained the investigators in the poster presentation.
When evaluating PFS by cytogenetic status, the investigative team found that patients with del(11q) treated with ibrutinib had a 97% reduction in the risk of disease progression or death when compared with those receiving chlorambucil; there was an 80% reduction noted in those without del(11q). More, the PFS rates for patients with del(11q) receiving ibrutinib and chlorambucil were 60% and 0%, respectively. For those without del(11q), corresponding rates were 61% and 13%.
The PFS rate for patients with unmutated IGHV was 62% with ibrutinib compared with 2% for chlorambucil. The rates for patients with mutated IGHV were 67% and 18% for ibrutinib and chlorambucil, respectively.
The OS rate in the overall population was significantly improved in the ibrutinib arm, with 78% of patients estimated to be alive at a follow-up of 6.5 years and a 49% reduction in the risk of death.
Outcomes of the open-label, multicenter, international included PFS, OS, overall response rate (ORR), and safety.
As for safety and adverse effects (AEs), the rates of discontinuations remained low for patients treated with ibrutinib. Patients discontinued first-line ibrutinib due to AEs (23%), disease progression (12%), death (8%), patient withdrawal (7%), and investigator decision (3%).
“Active dose management (dose holds and reductions) to address AEs enabled most patients who required dose management to continue benefiting from ibrutinib treatment,” wrote the investigators.
Nearly half of the patients remained on ibrutinib treatment for the investigative team follow-up at the 7-year mark.