Ibrutinib Plus Bendamustine and Rituximab Prolongs PFS Benefit in Newly Diagnosed MCL

Ibrutinib (Imbruvica) plus bendamustine and rituximab (Rituxan) could become the new standard of care in older patients with newly diagnosed mantle cell lymphoma (MCL), said Michael Wang, MD. He added that the combination elicited durable responses as frontline therapy in patients with MCL older than 65 years of age in primary findings from the phase 3 SHINE trial (NCT01776840).

“The SHINE trial was the first phase 3 clinical trial investigating ibrutinib in combination with bendamustine plus rituximab followed by rituximab maintenance,” Wang said.

In an interview with OncLive^®, Wang, professor, Department of Lymphoma & Myeloma, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discussed the innovative design of the SHINE trial, noted the importance of developing improved treatments for older patient populations, and highlighted significant progression-free survival (PFS) and safety data from the study.

OncLive^®: What was the rationale for the phase 3 SHINE trial?

Wang: The SHINE study was an international, randomized, phase 3 clinical trial that was conducted across 183 sites, looking at first-line treatment in elderly patients with MCL.

MCL is a type of non-Hodgkin lymphoma that develops from malignant B lymphocytes. Older patients with MCL often cannot tolerate intensive therapy and have poor outcomes. Bendamustine plus rituximab is the most commonly used therapy [in this setting], and literature has already evidenced that rituximab maintenance is useful after bendamustine plus rituximab.

In this clinical trial, we added ibrutinib [to the regimen of bendamustine plus rituximab followed by rituximab maintenance].

We enrolled 523 patients with newly diagnosed MCL. These were elderly patients over the age of 65. The experimental arm received ibrutinib plus 6 cycles of bendamustine and rituximab, then rituximab maintenance. Ibrutinib was administered until disease progression or treatment intolerance. In the placebo arm, patients received placebo plus 6 cycles of bendamustine and rituximab, followed by rituximab maintenance. Placebo was administered until treatment intolerance or disease progression.

What were the most important efficacy and safety results from the SHINE study?

This trial was successful because the primary end point of PFS was met. At a median follow-up of 7 years, the median PFS in the ibrutinib arm [was 80.6 months, or 6.7 years, compared with 52.9 months] in the placebo arm. This is a significant improvement. This benefit occurred within the first year, and it was durable with 7 years of follow up.

The adverse effects were similar in both arms. However, patients in the ibrutinib arm experienced higher incidences of rash and atrial fibrillation. The safety profile was tolerable.

What main point would you like your colleagues to glean from the findings of this trial?

The SHINE study data indicated that ibrutinib with bendamustine plus rituximab followed by rituximab maintenance [may become] the new standard of care for patients who are older than 65 years. [I hope to see this combination approved] globally.