Complete Response With Ibrutinib Plus BR Increases Likelihood of Prolonged PFS in Previously Untreated MCL

Treatment with ibrutinib (Imbruvica) plus bendamustine and rituximab (Rituxan; BR) increased the likelihood of achieving a complete response (CR) in patients with previously untreated mantle cell lymphoma (MCL), according to a post-hoc secondary efficacy analysis of the phase 3 SHINE (NCT01776840) trial.¹

Results showed that 65.5% of patients in the ibrutinib arm (n = 261) achieved a CR, while 24.1% achieved a partial response (PR) and 10.3% had stable disease (SD) or progressive disease (PD). Patients in the placebo arm (n = 262) of the trial achieved a CR, PR and SD or PD at respective rates of 57.6%, 30.9% and 11.5%.

Moreover, progression-free survival (PFS) was prolonged in patients who achieved a CR following treatment with either the ibrutinib combination or placebo plus BR.At a median follow up of 94.5 months, the median PFS for patients in the ibrutinib arm was 97.8 months (95% CI, 89.5-not evaluable) for those who achieved a CR, 27.6 months (95% CI, 12-34.8) for those who achieved a PR, and 2.9 months (95% CI, 2.4-10.3) for those who experienced SD and PD. The median PFS among patients in the placebo arm was 87.9 months (95% CI, 76.4-91.6), 16.7 months (95% CI, 13.8-19.8), and 3.4 months (95% CI, 2.2-8.3) for patients who achieved a CR, PR and SD or PD, respectively.

“This post-hoc secondary efficacy analysis of the SHINE study showed that prolonged PFS was more likely in patients with MCL who achieved CR, and that CR was more likely with ibrutinib plus BR than placebo plus BR,” said Yuko Mishima, MD, PhD.

Mishima is the vice director of the Hematology and Oncology Department at the Cancer Institute Hospital of the Japanese Foundation for Cancer Research in Tokyo, Japan.

What was the design of SHINE?

The trial enrolled patients who were at least 65 years old with a centrally confirmed diagnosis of MCL that was previously untreated and documented as stage 2 to 4 disease.² Patients also needed to have a measurable site of disease that was at least 1.5 cm in diameter, adequate organ function, and an ECOG performance status of 0 or 1.

If patients had planned stem cell transplantation, a history of stroke or intercranial hemorrhages or a cardiovascular disease that was clinically significant 6 months prior to screening, they were not included in the trial.^2,3

Eligible patients were randomly assigned to receive either a once daily, 560-mg dose of oral ibrutinib or placebo, in combination with bendamustine at 90 mg/m² body surface area on days 1 and 2 of each 28-day cycle and rituximab at 375 mg/m² body surface area on day 1 of each cycle.¹

Patients who achieved a CR or PR after 6 cycles of treatment continued to receive rituximab maintenance therapy once every 8 weeks for up to 12 additional doses. Treatment continued until disease progression or unacceptable toxicity.

The trial’s primary end point was PFS; secondary end points included CR, time to next treatment, overall survival (OS), objective response rate and minimal residual disease.³

In the current analysis, patients across both arms had a median age of 71 years and were mostly male (68.2% in ibrutinib arm; 71% in placebo arm).² Slightly more patients in each arm had an ECOG performance status of 0 (51.3%; 53.8%), and the majority of patients had extranodal bone marrow involvement (75.9%; 76.3%). Patients had a simplified mantle cell lymphoma international prognostic index (sMIPI) status of intermediate risk (47.5%; 49.1%), high risk (35.6%; 26.3%) or low risk (16.8%; 17.6%).

What were the additional data for ibrutinib plus bendamustine and rituximab from the analysis?

Investigators noted that similar trends in improved time to next treatment and OS following a CR were observed in the analysis.

Patients in the ibrutinib arm who achieved a CR, PR, and SD or PD had a median treatment duration of 43.17 months (range, 0.7-106.2), 9.69 months (range, 0.9-96.96) and 1.51 months (range, 0.2-3.2), respectively. In the placebo arm, median total treatment duration was were 55.92 months (range, 1.7-100.1), 13.86 months (range, 1.3-97.1) and 2 months (range, 0-12) in patients who achieved CR, PR, and SD or PD, respectively.

“The results of this post-hoc analysis suggest that CR is associated with better long-term disease control and improved survival outcomes in MCL,” Mishima added.

References

1. Mishima Y, Hashimoto D, Ichii M, et al. Impact of best response to ibrutinib plus bendamustine and rituximab on PFS in MCL: a secondary analysis of SHINE. Ann Hematol. 2025;104:4605–4610. https://doi.org/10.1007/s00277-025-06569-7
2. Wang M, Jurczak W, Jerkeman M, et al. Ibrutinib plus bendamustine and rituximab in untreated mantle-cell lymphoma. N Engl J Med. 2022;386(26):2482-2494. doi:10.1056/NEJMoa2201817
3. A study of the Bruton's Tyrosine Kinase inhibitor ibrutinib given in combination with bendamustine and rituximab in patients with newly diagnosed mantle cell lymphoma. Clinicaltrials.gov. Updated July 8, 2025. Accessed February 12, 2026.