Dr Habermann on the Withdrawal of U.S. Indications for Ibrutinib in MCL and MZL

Thomas M. Habermann, MD, consultant, Division of Hematology, Department of Internal Medicine, professor of medicine, Mayo Clinic, member, the Lymphoma Research Foundation’s Scientific Advisory Board, discusses the withdrawal of United States indications for ibrutinib (Imbruvica) in patients with mantle cell lymphoma (MCL) who have previously received at least 1 therapy and in those with marginal zone lymphoma (MZL) who require systemic treatment and have received at least 1 prior anti–CD20-based therapy.

In April 2023, AbbVie announced its intention to voluntarily withdraw ibrutinib in these 2 indications in the United States. No other indications for ibrutinib were affected. The decision was made following results of the phase 3 SHINE trial (NCT01776840) in patients with MCL and phase 3 SELENE (NCT01974440) trial in patients with indolent non-Hodgkin lymphoma, including follicular lymphoma and MZL.

Both SHINE and SELENE served as confirmatory trials following accelerated FDA approvals for ibrutinib for these 2 indications. Findings from SHINE published in New England Journal of Medicine showed that although the study met its primary end point of progression-free survival (PFS), the combination of ibrutinib and chemoimmunotherapy was associated with more toxicity vs chemoimmunotherapy alone, Habermann begins. Although full data from SELENE have not yet been published, the study failed to meet it primary end point of PFS, Habermann notes.

SHINE included patients with previously untreated MCL, and SELENE enrolled previously treated patients with follicular lymphoma patients and MZL, Habermann adds. SHINE evaluated ibrutinib in combination with bendamustine (Treanda) and rituximab (Rituxan) vs bendamustine and rituximab alone. SELENE examined ibrutinib in combination with bendamustine and rituximab, or in combination with R-CHOP. Both trials were placebo controlled and both had PFS as the primary end point.