Abstract
Mantle cell lymphoma (MCL) is a rare B-cell non-Hodgkin lymphoma with multiple subtypes including classical mantle cell lymphoma (cMCL), the leukemic variant of mantle cell lymphoma (LV-MCL), and in situ mantle cell neoplasia (ISMCN). Their clinical presentations differ significantly and range from indolent to very aggressive. The defining genetic feature and chief oncogenic mechanism of MCL involves the t(11;14)(q13;q32) translocation, which results in a fusion of the gene that encodes cyclin D1 (CCND1) and the immunoglobulin heavy chain gene (IGH). As a result of significant variation between subtypes, treatment approaches and prognoses of this disease vary drastically. Current treatment options for MCL range from observation to conventional chemotherapy with or without subsequent stem cell transplantation, to targeted immunotherapies against key molecular targets. The role of stem cell transplant has become more debatable for frontline consolidation therapy. Earlier incorporation of Bruton's tyrosine kinase (BTK) inhibitors is being strongly considered for frontline therapy. Chimeric antigen receptor therapy (CAR-T) therapies have become established treatment options for relapsed/refractory disease. Ongoing frontiers involve optimal management of TP53 mutated MCL and those relapsing with CNS involvement. Novel therapeutic approaches including the development of non-covalent BTK inhibitors and bispecific antibody therapy carry significant promise to further improve outcomes across all subtypes of this disease.
Overview
- The study focuses on mantle cell lymphoma (MCL), a rare B-cell non-Hodgkin lymphoma with multiple subtypes, and examines the clinical presentations, treatment options, and prognoses of this disease.
- The study highlights the significance of the t(11;14)(q13;q32) translocation in MCL, which results in the fusion of the cyclin D1 gene and the immunoglobulin heavy chain gene, leading to the overexpression of cyclin D1.
- The primary objective of the study is to summarize the current understanding of MCL, its subtypes, and available treatment options, with the goal of improving patient outcomes.
Comparative Analysis & Findings
- The study compares the clinical presentations and treatment outcomes of different MCL subtypes, including classical mantle cell lymphoma (cMCL), leukemic variant of mantle cell lymphoma (LV-MCL), and in situ mantle cell neoplasia (ISMCN).
- Findings suggest that treatment approaches and prognoses vary significantly between MCL subtypes, emphasizing the importance of subtype-specific treatment strategies.
- CAR-T therapies have become established treatment options for relapsed/refractory MCL, while BTK inhibitors are being considered for frontline therapy, and novel approaches such as non-covalent BTK inhibitors and bispecific antibody therapy hold promise.
Implications and Future Directions
- The study highlights the need for improved management of TP53 mutated MCL and those relapsing with CNS involvement, as these patient populations require more effective treatment strategies.
- The role of stem cell transplant in frontline consolidation therapy is becoming more debatable, and earlier incorporation of BTK inhibitors and CAR-T therapies may improve patient outcomes.
- Further research is needed to develop more effective treatment strategies for MCL, including the optimization of novel therapeutic approaches and the identification of predictive biomarkers for treatment response.