Recent advances in targeted therapies have the potential for major impacts on treatment practices for mantle cell lymphoma (MCL), according to a recent review published in Pharmaceuticals (2017;10(1):28).
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The treatment landscape for MCL has evolved in recent years toward upfront intensive strategies, such as autologous stem cell transplantation, but effective maintenance therapies are still needed to improve disease outcomes and lessen the risk of relapse. Targeted drugs have undergone significant clinical investigation to improve the safety and efficacy of maintenance therapy in this setting.
Researchers from the Fred Hutchinson Cancer Research Center at the University of Washington conducted a review of the currently available targeted therapies and their roles in improving outcomes after autologous stem cell transplantation for MCL. Aside from the standard of care with maintenance rituximab, researchers analyzed other anti-CD20 monoclonal antibodies, radioimmunotherapy, proteosome inhibitors, Bruton’s tyrosine kinase (BTK) inhibitors, lenalidomide, and various combinations as leaders in targeted therapies.
Maintenance rituximab after autologous stem cell transplantation offers a survival advantage for patients with MCL, but may cost an excess of $5000 per dose and require up to 18 doses. Thus, current research has been aimed to create newer anti-CD20 monoclonal antibodies that overcomes these challenges. Ofatumumab and obinutuzumab are fully humanized anti-CD20 antibodies that have proven efficacy in certain B-cell malignancies and have exhibited promising results in preclinical data for MCL. Ongoing studies are examining obinutuzumab as a maintenance option for patients with MCL after autologous stem cell transplantation.
Radioimmunotherapy efforts have focused on ibritumomab tiuxetan, which is approved for indolent B-cell malignancies in the salvage and consolidation settings. Research has led many to believe that ibritumomab tiuxetan may prove valuable as a pre-maintenance option followed by anti-CD20 immunotherapy maintenance in high-risk MCL.
Researchers also note that proteosome inhibitors (bortezomib), BTK-inhibitors (ibrutinib), and lenalidomide are serviceable options in the maintenance setting for MCL, though these options are costlier and may increase the risk of serious adverse events. Nonetheless, ibrutinib and lenalidomide are generally well-tolerated and proven to be efficacious.
Researchers conclude that results of ongoing studies involving anti-CD20 monoclonal antibodies, radioimmunotherapy, BTK-inhibitors, proteosome inhibitors, and lenalidomide are poised to impact the MCL treatment landscape significantly. Results in the coming years will “guide further research efforts, including MRD-stratification of initiation and duration of treatment, biomarker-based selection of therapy, and rational therapeutic sequencing or combinations,” they wrote. – Zachary Bessette
