Findings from the phase 3 SHINE trial showed that ibrutinib combined with bendamustine plus rituximab and rituximab maintenance significantly improved progression-free survival (PFS) compared with standard chemoimmunotherapy in patients aged ≥65 years with untreated mantle cell lymphoma (MCL). These data were presented at the 2022 ASCO Annual Meeting.

“Elderly patients with MCL are unsuitable for intensive chemotherapy or transplantation due to excessive toxicities,” wrote lead investigator Michael Wang, MD, University of Texas MD Anderson Cancer Center, Houston, and colleagues, who conducted the trial of 523 patients enrolled between May 2013 and November 2014 from 183 sites across all geographical regions.

The patients (median age, 71 years) were stratified based on whether they were low-, intermediate-, or high-risk and randomized in a 1:1 ratio to receive ibrutinib 560 mg daily or placebo plus 6 cycles of bendamustine 90 mg/m² plus rituximab 375 mg/m². The primary end point of the study was PFS.

A total of 261 patients received ibrutinib and bendamustine plus rituximab while 262 were given placebo and bendamustine plus rituximab. Rituximab maintenance therapy was given to patients who achieved an objective response every 8 weeks for up to 12 additional doses, and ibrutinib and placebo were administered until disease progression or unacceptable toxicity occurred.

At the point of primary analysis (median follow-up, 84.7 months) the primary end point was met as PFS was significantly improved in the ibrutinib versus placebo arm (hazard ratio, 0.75; one-sided P = .011); the median PFS was 80.6 months versus 52.9 months for each arm and the complete response rate was 65.5% versus 57.6% (P = .0567), respectively.

Overall survival rates did not differ between the treatment arms (P = .648), but time-to-next treatment was longer in the ibrutinib versus placebo arm (P <.001). Of note, 52 (19.9%) and 106 (40.5%) patients received subsequent anti-lymphoma therapy in the ibrutinib and placebo arms, respectively, and 41 (38.7%) of the 106 patients in the placebo arm received a second-line Bruton’s tyrosine kinase inhibitor.

Grade 3 or 4 treatment-emergent adverse events were documented at rates of 81.5% for the ibrutinib arm and 77.3% for the placebo arm, with atrial fibrillation reported in 13.9% and 6.5% of patients, respectively. Quality of life was similar for both arms, as were rates of major hemorrhage, hypertension, arthralgia, and secondary primary malignancies.

“This phase 3 study in untreated MCL demonstrated that ibrutinib combined with bendamustine plus rituximab and rituximab maintenance significantly improved PFS compared with standard chemoimmunotherapy, with a median PFS of 6.7 years,” reported Dr Wang et al.

“The safety profile was consistent with the known profiles of the individual drugs,” they concluded.

Source:

Wang M, Jurczak W, Jerkeman M, et al. 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). Presented at: the 2022 ASCO Annual Meeting; June 3-7, 2022; Chicago, IL. Abstract LBA7502.