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Tx Selection and Optimization in MCL

CME

Treatment Selection and Optimization in MCL From a European Union Perspective

Physicians: Maximum of 1.00 AMA PRA Category 1 Credit™

Released: April 15, 2025

Expiration: October 14, 2025

Mats Jerkeman
Mats Jerkeman, MD, PhD
CME/CE Information

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Background

MCL is a rare form of non-Hodgkin lymphoma (NHL), accounting for 5% to 7% of all NHL in Western Europe.1,2 It is less common in Asian countries. Although the clinical presentation of MCL varies from indolent to very aggressive forms, it is mostly aggressive. It is characterized by t(11;14) which leads to the overexpression of cyclin D1. The median age at diagnosis is approximately 70 years. The majority of patients with MCL are males, accounting for approximately 75% to 80% of patients with the disease. Typically, MCL is diagnosed in the advanced stage with extranodal involvement of sites such as the bone marrow, gastrointestinal tract, and spleen. The disease is often initially responsive to therapy, but in most cases patients experience multiple relapses. At present, it is unclear if any patient with MCL can truly be cured of the disease.

MCL Pathogenesis

MCL originates from naive B-cells, where cyclin D1 translocation occurs. The cells may then develop into in situ mantle cell neoplasia, probably in the mantle zone of the germinal center.2 Thereafter, it can acquire somatic hypermutation, proceed through the germinal center and develop into the leukemic non-nodal subtype of MCL. More commonly, the naive B-cell can avoid the germinal center, acquire additional genetic aberrations, and develop into the more common classical subtype of MCL that usually presents with nodal disease in addition to extranodal disease involving the bone marrow. Subsequently, it can acquire additional genetic aberrations such as TP53 alterations and other oncogenic abnormalities and progress into more aggressive MCL subtypes with blastoid or pleomorphic histology.

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NCCN Guidelines: Diagnostic Workup in MCL

Essential diagnostic workup to determine whether a patient has MCL includes a physical examination with attention to peripheral lymph nodes and the Waldeyer’s ring.3 Of note, the determination of the complete blood count with differential is critical because many patients present with lymphocytosis. The determination of lactate dehydrogenase levels is an important prognostic factor in MCL, and the diagnostic workup should include radiologic examinations using PET/CT imaging with contrast. If this is not possible, a CT scan of the neck, thorax, and abdomen can be performed. In some cases such as for patients with possible limited-stage MCL, an endoscopy and a bone marrow biopsy with aspirate can be done to confirm the presence of localized disease.

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Risk Factors in MCL

MCL is a biologically heterogenous disease, and there are several important biologic risk factors that are also critical for treatment decision-making. Factors associated with a favorable outcome include a low proliferation rate with Ki-67 expression of 10% or less and the presence of a stable karyotype.4 Patients with hypermutated IGHV and SOX-11 negativity have a better prognosis.

An important high-risk factor is the presence of nonclassical histology, specifically the blastoid and pleomorphic MCL subtypes. A high proliferation rate with Ki-67 expression greater than 30% is also a poor prognostic factor. Perhaps the most important high-risk factor associated with poor prognosis is the presence of a TP53 mutation. In addition, the presence of a complex karyotype is a poor prognostic factor for patients with MCL. Although the treatment outcome for patients with MCL has considerably improved over the last 2 decades or so, there is still no identified curative treatment for this disease.

Currently, the most important knowledge gap is figuring out how to treat patients with high-risk disease, especially those with a TP53 mutation or p53 protein overexpression, as there is currently no clear solution or consensus. Fortunately, with the introduction and integration of novel agents and approaches into the treatment algorithm, we have seen significant improvements upon the conventional standard of care, immunochemotherapy.

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