Ibrutinib combined with bendamustine-rituximab improved progression-free survival (PFS) by 50% for older patients with newly diagnosed mantle cell lymphoma when compared with patients who received a placebo plus bendamustine-rituximab, according to new research reported at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting.

Researchers studied 523 patients with mantle cell lymphoma at 203 international study locations. The double-blind phase III SHINE trial randomly assigned these patients, all aged ≥ 65 years, to either ibrutinib plus bendamustine-rituximab (n = 261) or placebo plus bendamustine-rituximab (n = 262). Both study groups had similar baseline characteristics. The median age of the patients in the study was 71 years. The median time that the patients were followed was seven years.

Median PFS was 80.6 months with ibrutinib in combination with bendamustine-rituximab and rituximab maintenance, a 50% improvement over the group that received a placebo with bendamustine-rituximab and rituximab maintenance, which saw a median PFS of 52.9 months. The complete response rate was 65.5% in the ibrutinib group and 57.6% in the placebo group. There was no difference in OS between treatment groups at the time of the latest assessment of outcomes.

The time to the next treatment was longer in the ibrutinib arm compared with the placebo arm. The number of patients who needed a next treatment was lower in the ibrutinib group compared with the placebo group: 52 (19.9%) and 106 (40.5%) patients received subsequent anti-lymphoma therapy in the ibrutinib and placebo groups, respectively; 41 out of the 106 patients (38.7%) in the placebo group received a subsequent Bruton tyrosine kinase inhibitor (mostly ibrutinib).

Grade 3 or 4 adverse events during treatment were 81.5% and 77.3% in the ibrutinib vs. placebo groups, respectively. The safety profile of the combined treatment was consistent with the known profiles of ibrutinib and bendamustine-rituximab. Quality of life was similar in both groups.

“The SHINE study is the first international phase III trial to show a positive impact of ibrutinib combined with standard-of-care treatment in this disease. The progression-free survival is substantially longer than the common treatment options used today, which is an important clinical advancement,” said lead author Michael Wang, MD, University of Texas MD Anderson Cancer Center in Houston. 

Wang S, Jurczak W, Jerkeman M. Primary results from the double-blind, placebo-controlled, phase III SHINE study of ibrutinib in combination with bendamustine-rituximab (BR) and R maintenance as a first-line treatment for older patients with mantle cell lymphoma (MCL). Abstract presented at: ASCO Annual Meeting; June 3-7, 2022; Chicago, IL, and virtual. Abstract LBA7502.