AbbVie, Janssen Withdraw Imbruvica Accelerated Approvals for MCL, MZL

Over half of evaluable patients who received an infusion of tisagenlecleucel achieved response.
Credit: Shutterstock.
The withdrawal of MCL and MZL indication does not affect the other approved indications for Imbruvica.

Janssen and AbbVie are voluntarily withdrawing the accelerated approvals of Imbruvica® (ibrutinib) for mantle cell lymphoma (MCL) in patients who have received at least 1 prior therapy, and for marginal zone lymphoma (MZL) in patients who require systemic therapy and have received at least 1 prior anti-CD20-based therapy, due to requirements related to accelerated approval status granted by the Food and Drug Administration (FDA).

Under the accelerated approval pathway, continued approval of both of these indications was contingent upon verification and description of clinical benefit in confirmatory trials. The phase 3 SHINE study ( Identifier: NCT01776840) and the phase 3 SELENE study ( Identifier: NCT01974440) served as confirmatory studies for the MCL and MZL indications, respectively.

In the SHINE study, patients 65 years and older with untreated MCL were randomly assigned to receive ibrutinib or placebo, in combination with bendamustine and rituximab. Results showed that treatment with ibrutinib significantly prolonged progression-free survival (PFS) compared with placebo (80.6 months vs 52.9 months; hazard ratio, 0.75; 95% CI, 0.59-0.96; P =.01); however, overall survival was found to be similar between the groups. The addition of ibrutinib to chemoimmunotherapy was associated with increased adverse reactions.

The randomized, double-blind, placebo-controlled SELENE study compared ibrutinib to placebo in combination with bendamustine and rituximab (BR) or rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in patients with previously untreated MZL. According to the Companies, the study did not meet its primary endpoint of PFS. Additional information from the SELENE trial will be presented at a future medical meeting.

Following a review of the data, the FDA concluded that the primary outcomes from these confirmatory studies were considered insufficient to support conversion to full approval.

“We pursued accelerated approvals for MCL and MZL indications for Imbruvica in the US to offer a treatment to patients who at the time had limited therapeutic options,” said Roopal Thakkar, senior vice president, chief medical officer, AbbVie. “While we are disappointed in the outcome of the confirmatory trials for these indications, we remain confident in the benefit/risk profile of Imbruvica for patients living with multiple forms of blood cancer around the world.”

The withdrawal of the MCL and MZL indications does not affect the other approved indications for Imbruvica.


  1. Update on Imbruvica® (ibrutinib) US accelerated approvals for mantle cell lymphoma and marginal zone lymphoma indications. News release. AbbVie. April 6, 2023.
  2. Wang ML, Jurczak W, Jerkeman M, et al. Ibrutinib plus bendamustine and rituximab in untreated mantle-cell lymphoma. New England Journal of Medicine. Published online June 30, 2022. doi:10.1056/NEJMoa2201817