Mantle cell lymphoma – advances in molecular biology, prognostication and treatment approaches

Abstract

Mantle cell lymphoma (MCL) is clinically characterised by its heterogenous behaviour with courses ranging from indolent cases that do not require therapy for years to highly aggressive MCL with a very limited prognosis. A better understanding of the complex biology of MCL has already led to the approval of several innovative agents, expanding the landscape of MCL therapies and improving therapeutic options especially for refractory/relapsed (R/R) disease.Nevertheless, to further optimise MCL treatment, early identification of individual risk profile and risk-adapted, patient-tailored choice of therapeutic strategy needs to be prospectively incorporated into clinical patient management. The present review highlights recent advances in deciphering the molecular background of MCL, the definition of prognostically relevant factors and the identification of potential druggable targets and summarises current treatment recommendations for primary and R/R MCL including novel targeted therapies.

Real-world treatment and outcome patterns of patients with mantle cell lymphoma in China: a large, multicenter retrospective analysis

“…MCL often occurs in male patients in the Asian population, and the median age at initial presentation is 60 years, which is signi cantly lower than that in Western and American countries. In pathological subtypes, compared with previous reports, 10-15% of patients present with a more indolent subtype, non-nodular mantle cell lymphoma only accounted for 3.3% in our corhort and the majority of these patients have symptoms and treatment indications (19). Most newly diagnosed patients display aggressive disease features, blastic/pleomorphic mantle cell lymphoma accounted for 12.8%, ki-67 ≥ 30% was 57.7% and ki-67 ≥ 50% was 26.1%.…”

“…The standard frontline therapy for MCL is not completely uni ed, however, there is a general consensus that cytarabine-containing chemotherapy combined with autologous hematopoietic stem cell transplantation as the rst-line treatment for young and t patients, whereas older or un t patients are treated with combination chemo-immunotherapy according to different tolerance (9,(20)(21)(22)(23). Although the bene t of high-dose cytarabine is clear, due to different clinical trial results, the recognized uni ed regimen is not de nite.…”

How to Diagnose and Treat CD5-Positive Lymphomas Involving the Spleen

“…Adequate patient stratification, the usage of aggressive ICT regimens in young patients and rituximab maintenance together with new agents at relapse contributed to improved survival rates. Nevertheless, the long-term prognosis is still poor [ 76 ].…”

“…Although the majority of MCL patients pursue an aggressive clinical course requiring immediate treatment, several investigators identified indolent forms of disease representing 10–15% of cases [ 34 ]. As mentioned above, these include not only the leukemic/non-nodal, SOX11-negative form but also rare, asymptomatic, nodal/extra-nodal forms with a low tumor burden, classical morphology on histopathology, low proliferation rate and an intact TP53 [ 51 , 76 ]. It was shown that these subsets may remain stable for years and that early treatment does not impact overall survival [ 77 , 78 ].…”

“…However, very active BTK inhibitors (BTKi), of which Ibrutinib [ 78 , 85 , 87 ] and Acalabrutinib [ 88 ] are approved, currently dominate the therapeutic strategies. Numerous clinical trials are testing the combination of new agents with chemotherapy at the first line, the addition of lenalidomide or bortezomib to maintenance regimens and the use of new agents in comparison to chemotherapy [ 72 , 76 ]. The future inclusion of BTKi in first-line regimens will change the treatment of relapsed disease.…”