Janssen and AbbVie are withdrawing the accelerated approvals of Imbruvica (ibrutinib) for mantle cell lymphoma (MCL) and marginal zone lymphoma (MZL) after phase 3 trials failed to show clinical benefits from Imbruvica treatment in MZL and MCL.

The US Food and Drug Administration (FDA) granted Imbruvica accelerated approval in 2013 to treat MCL patients who had received at least 1 prior therapy. In 2017, the drug was granted accelerated approval to treat MZL in patients who required systemic therapy and had received at least 1 prior anti-CD20-based therapy.

Both approvals were based on overall response rates in phase 2 trials. The continued approval for both indications was contingent upon verification of clinical benefit in confirmatory trials. After reviewing data from these trials, the FDA concluded that this requirement was not met, and the trials’ primary outcomes did not support converting the accelerated approvals to full approvals.

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The phase 3 SHINE study (ClinicalTrials.gov Identifier: NCT01776840) was the confirmatory trial for MCL, and the phase 3 SELENE study (ClinicalTrials.gov Identifier: NCT01974440) was the confirmatory trial for MZL.

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. 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. Furthermore, the addition of ibrutinib to chemoimmunotherapy was associated with an increase in adverse events.

The randomized, double-blind SELENE study was designed to compare 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.

“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 and chief medical officer of 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.


Update on Imbruvica® (ibrutinib) US accelerated approvals for mantle cell lymphoma and marginal zone lymphoma indications. News release. AbbVie. April 6, 2023. https://news.abbvie.com/news/press-releases/update-on-imbruvica-ibrutinib-us-accelerated-approvals-for-mantle-cell-lymphoma-and-marginal-zone-lymphoma-indications.htm.

Wang ML, Jurczak W, Jerkeman M, et al. Ibrutinib plus bendamustine and rituximab in untreated mantle-cell lymphoma. N Engl J Med. Published online June 30, 2022. doi:10.1056/NEJMoa2201817

This article originally appeared on MPR