Dr Habermann on Data Leading to the Withdrawal of Ibrutinib in MCL

Thomas M. Habermann, MD, consultant, Division of Hematology, Department of Internal Medicine, professor of medicine, Mayo Clinic, member, the Lymphoma Research Foundation’s Scientific Advisory Board, discusses the data that led to the decision to withdraw the indication for ibrutinib (Imbruvica) for the treatment of patients with mantle cell lymphoma (MCL).

In April 2023, AbbVie announced the intention to voluntarily withdraw indications for ibrutinib for the treatment of patients with MCL who have previously received at least 1 therapy and in those with marginal zone lymphoma (MZL) who require systemic treatment and have received at least 1 prior anti–CD20-based therapy. This decision was based on data from the phase 3 SHINE trial (NCT01776840) for MCL and the phase 3 SELENE trial (NCT01974440) for MZL.

Ibrutinib had received accelerated approval for the treatment of patients with MCL based on the overall response rate (ORR) observed in the phase 2 Study 1104 trial (NCT01236391). In the single-arm study, patients were treated with 560 mg of oral ibrutinib daily, and in 111 patients, the BTK inhibitor elicited an ORR of 65.8% (95% CI, 56.2%-74.5%), including a complete response rate of 17.1%.

SHINE served as a confirmatory trial for the accelerated approval for the MCL indication. The study was conducted the frontline setting for patients with MCL, who were randomly assigned to receive ibrutinib or placebo in combination with bendamustine and rituximab (Rituxan).

Data from SHINE showed that at a median follow-up of 84.7 months (range, 0.1-97.5), the median progression-free survival (PFS) was 80.6 months (95% CI, 61.9–not evaluable) for the ibrutinib arm vs 52.9 months (95% CI, 43.7-71.0) for the placebo arm, meeting the primary end point of the trial (stratified HR, 0.75; 95% CI, 0.59-0.96; P = .01). Although the PFS benefit was observed across the majority of prespecified subgroups for the ibrutinib regimen, those with a simplified MIPI score of high risk and those whose tumors harbored TP53 mutations did not derive a clear benefit.

However, the ORR was 89.7% in the ibrutinib arm and 88.5% in the placebo arm. Overall survival (OS) was comparable between the 2 arms (HR, 1.07; 95% CI, 0.81-1.40). Additionally, the rates of grade 3/4 adverse effects were 81.5% in the ibrutinib arm vs 77.3% in the control arm.