A Systematic Review of the Efficacy of Ibrutinib-Based Combination Therapy for Mantle-Cell Lymphoma

The mantle-cell lymphoma (MCL) treatment landscape is moving toward the use of orally administered nonchemotherapeutic agents in the frontline and relapsed/refractory settings. Newer approaches are investigating whether Bruton’s tyrosine kinase (BTK) inhibitors and/or venetoclax given in combination with anti-CD20 monoclonal antibodies can replace chemoimmunotherapy as a safe and effective frontline treatment option. In addition, researchers are investigating the role of anti-CD19 CAR T-cells as potential consolidation therapy in high-risk MCL.1

Despite advances, treatment for relapsed/refractory MCL continues to be challenging. Here, researchers sought to determine the efficacy of the BTK inhibitor ibrutinib in combination therapy for newly diagnosed and relapsed/refractory MCL, using a systematic database review.

Eleven studies with 363 patients were identified, all of which included ibrutinib given in combination with 1 or 2 other agents. Two trials studied ibrutinib in combination with rituximab, and 2 studied ibrutinib in combination with venetoclax. Ibrutinib was also studied as part of 3-drug combination regimens with bendamustine plus rituximab, lenalidomide plus rituximab, and obinutuzumab plus venetoclax, respectively. Ibrutinib was also studied in combination with other drugs, such as palbociclib, ublituximab, and bortezomib, as part of 2-drug combination regimens. Most studies included patients with relapsed/refractory disease. Objective response rate (ORR) was the primary end point for all the trials in the database review.

Several studies showed impressive efficacy; however, the combination of ibrutinib plus rituximab had the highest ORR (100%) and complete response (CR; 80%) in patients with newly diagnosed MCL. The combination of ibrutinib plus venetoclax and obinutuzumab demonstrated the highest overall ORR (89%) and CR (78%) in the treatment of patients with relapsed/refractory MCL, followed by ibrutinib plus rituximab (ORR, 88%; CR, 44%), ibrutinib plus lenalidomide plus rituximab (ORR, 83%; CR, 41%), and ibrutinib plus ublituximab (ORR, 87%; CR, 33%). In the studies, adverse events included cytopenia, atrial fibrillation, septic shock, tumor lysis syndrome, and gastrointestinal toxicities. Although additional studies are needed to further assess and confirm the role of ibrutinib, these studies suggest that ibrutinib will likely play a role as a backbone of combination treatment in newly diagnosed and relapsed/refractory MCL for some time to come. 

Abstract e19043; Thirunagari P, et al.


  1. Jain P, Wang M. Mantle cell lymphoma: 2019 update on the diagnosis, pathogenesis, prognostication, and management. Am J Hematol. 2019;94:710-725.

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