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Journal Article
Review
Mantle cell lymphoma and its management: where are we now?
Mantle cell lymphoma is a relatively new recognized hematological malignant disease, comprising of 2.5-6% non-Hodgkin's lymphomas. The complexity of its clinical presentations (nodular pattern, diffuse pattern, and blastoid variant), variety in disease progression, and treatment response, make this disease a research focus to both experimental oncology and clinical oncology. Overexpression of cyclin D1 and chromosome t(11,14) translocation are the known molecular biomarkers of this disease. Mantle cell international prognostic index (MIPI), ki-67 proliferation index, and TP53 mutation are emerging as the prognostic biomarkers. Epigenetic profile variance and SOX11 gene expression profile correlate with treatment response. Over the years, the treatment strategy has been gradually evolving from combination chemotherapy to combination of targeted therapy, epigenetic modulation therapy, and immunotherapy. In a surprisingly short period of time, FDA specifically approved 4 drugs for treating mantle cell lymphoma: lenalidomide, an immunomodulatory agent; Bortezomib, a proteasome inhibitor; and Ibrutinib and acalabrutinib, both Bruton kinase inhibitors. Epigenetic agents (e.g. Cladribine and Vorinostat) and mTOR inhibitors (e.g. Temsirolimus and Everolimus) have been showing promising results in several clinical trials. However, treating aggressive variants of this disease that appear to be refractory/relapse to multiple lines of treatment, even after allogeneic stem cell transplant, is still a serious challenge. Developing a personalized, precise therapeutic strategy combining targeted therapy, immunotherapy, epigenetic modulating therapy, and cellular therapy is the direction of finding a curative therapy for this subgroup of patients.
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