Mantle cell lymphoma: 2019 update on the diagnosis, pathogenesis, prognostication, and management

Abstract

Unprecedented advances in our understanding of the pathobiology, prognostication, and therapeutic options in mantle cell lymphoma (MCL) have taken place in the last few years. Heterogeneity in the clinical course of MCL—indolent vs aggressive—is further delineated by a correlation with the mutational status of the variable region of immunoglobulin heavy chain, methylation status, and SOX‐11 expression. Cyclin‐D1 negative MCL, in situ MCL neoplasia, and impact of the karyotype on prognosis are distinguished. Apart from Ki‐67% and morphology pattern (classic vs blastoid/pleomorphic), the proliferation gene signature has helped to further refine prognostication. Studies focusing on mutational dynamics and clonal evolution on Bruton's tyrosine kinase (BTK) inhibitors (ibrutinib, acalabrutinib) and/or Bcl2 antagonists (venetoclax) have further clarified the prognostic impact of somatic mutations in TP53, BIRC3, CDKN2A, MAP3K14, NOTCH2, NSD2, and SMARCA4 genes. In therapy, long‐term follow‐up on chemo‐immunotherapy studies has demonstrated durable remissions in some patients; however, long‐term toxicities, especially from second cancers, are a serious concern with chemotherapy. The therapeutic options in MCL are constantly evolving, with dramatic responses from nonchemotherapeutic agents (ibrutinib, acalabrutinib, and venetoclax). Chimeric antigen receptor therapy and combinations of nonchemotherapeutic agents are actively being studied and our focus is shifting toward making the treatment of MCL chemotherapy‐free. Still, MCL remains incurable. The following aspects of MCL continue to pose a challenge: disease transformation, role of the cytokine‐microenvironmental milieu, incorporation of positron emission tomography‐computerized tomography imaging, minimal residual disease in the prognosis, circulating tumor DNA testing for clonal evolution, predicting resistance to BTK inhibitors, and optimal management of patients who progress on BTK/Bcl2 inhibitors. Next‐generation clinical trials should incorporate nonchemotherapeutic agents and personalize the treatment based upon the genomic profile of individual patient. Recent advances in the field of MCL are reviewed.

Concurrent TP53 and CDKN2A Gene Aberrations in Newly Diagnosed Mantle Cell Lymphoma Correlate with Chemoresistance and Call for Innovative Upfront Therapy

“…Mantle cell lymphoma (MCL) represents a subtype of non-Hodgkin lymphoma with poor prognosis, especially for patients who are resistant to front-line treatment [1][2][3][4][5]. Besides the translocation t (11;14), several recurrent cytogenetic aberrations have been reported [6][7][8][9][10][11][12][13].…”

Endovascular Repair for Abdominal Aortic Rupture Caused by Periaortic Mantle Cell Lymphoma

“…1) MCL is a relatively uncommon subtype of non-Hodgkin lymphoma that is associated with poor prognosis due to aggressive clinical course, low sensitivity to traditionally used chemotherapy, and high relapse rates. 2) Several clinical cases of aortic aneurysms and ruptures, or aortic dissections due to secondary invasion by periaortic lymphoma have been previously reported. 3,4) According to those previous reports, underlying mechanisms of aneurysmal degeneration or rupture in patients with periaortic lymphoma were attributed to direct invasion or compression of the aortic wall by lymphoma tissues.…”

Mantle cell lymphoma may have a different clinical course in Mexican Mestizos: Real-world data from a single center

“…Mantle cell lymphoma (MCL) is a rare and aggressive disease which accounts for approximately 5% of all B-cell non-Hodgkin's lymphomas (NHL) 1 . The incidence of MCL is higher in non-Hispanic Whites in the United States 2,3 . There is very limited information about this variant of NHL in México 4 .…”