What is mantle cell lymphoma (MCL)?

From the Guidelines

Mantle cell lymphoma is a rare and aggressive type of non-Hodgkin lymphoma characterized by the overproduction of cyclin D1 protein due to a genetic mutation, typically affecting older adults and requiring prompt treatment with combination chemotherapy regimens such as R-CHOP or R-hyperCVAD, and potentially stem cell transplantation or targeted therapies like ibrutinib or venetoclax. Mantle cell lymphoma usually develops in the outer edge of lymph nodes called the mantle zone and is more common in men than women, with symptoms including swollen lymph nodes, fatigue, night sweats, unexplained weight loss, and abdominal pain or bloating from enlarged spleen or liver 1. The disease is typically diagnosed in individuals around the age of 60, with a median age of 65 years at first diagnosis, as noted in the ESMO clinical practice guidelines for diagnosis, treatment, and follow-up of newly diagnosed and relapsed mantle cell lymphoma 1. Key characteristics of mantle cell lymphoma include:

• Overproduction of cyclin D1 protein due to a genetic mutation where chromosomes 11 and 14 exchange material
• Typically affects older adults, with a median age of 65 years at diagnosis
• More common in men than women
• Symptoms include swollen lymph nodes, fatigue, night sweats, unexplained weight loss, and abdominal pain or bloating from enlarged spleen or liver
• Treatment typically involves combination chemotherapy regimens such as R-CHOP or R-hyperCVAD, and potentially stem cell transplantation or targeted therapies like ibrutinib or venetoclax, as recommended in the ESMO guidelines 1. Some of the recommended treatment approaches for mantle cell lymphoma include:
• R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) for elderly patients or those with compromised health
• R-hyperCVAD (rituximab plus hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone) alternating with high-dose methotrexate and cytarabine for younger, fitter patients
• Stem cell transplantation for eligible patients
• Targeted therapies like ibrutinib or venetoclax for patients with relapsed or refractory disease, as supported by studies such as those cited in the ESMO guidelines 1. It is essential to note that mantle cell lymphoma is generally considered incurable but treatable, with a median survival of 5-7 years, though outcomes vary widely based on individual factors, such as age, overall health, and response to treatment, as discussed in the ESMO guidelines 1.

From the FDA Drug Label

The simplified MIPI (Mantle Cell Lymphoma International Prognostic Index) score was low in 33%, intermediate in 43%, and high in 24% of patients. A total of 38% of patients had tumor bulk ≥ 5 cm and 86% had Ann Arbor stage IV disease The median time since diagnosis was 46. 3 months and the median number of prior treatments was 2 (range 1 to 5), including 18% with prior stem cell transplant. At baseline, 37% of patients had at least one tumor with a longest diameter ≥ 5 cm, 73% had extra nodal involvement including 51% with bone marrow involvement.

Mantle cell lymphoma (MCL) is a type of cancer that is characterized by:

• Tumor bulk: 38% of patients had tumor bulk ≥ 5 cm
• Ann Arbor stage: 86% had stage IV disease
• Extra nodal involvement: 73% had extra nodal involvement, including 51% with bone marrow involvement
• Prior treatments: median number of prior treatments was 2 (range 1 to 5)
• Prognostic index: simplified MIPI score was low in 33%, intermediate in 43%, and high in 24% of patients 2

From the Research

Definition and Characteristics of Mantle Cell Lymphoma

• Mantle cell lymphoma (MCL) is a distinct subtype of non-Hodgkin's lymphoma, characterized by the involvement of the lymph nodes, spleen, blood, and bone marrow 3, 4.
• It is a heterogeneous disease with variable biologic and clinical behavior, and has historically been associated with a poor prognosis 3, 5.
• MCL is characterized by a chromosomal translocation t(11;14) resulting in the overexpression of cyclin D1, which is detected by immunohistochemistry in 98% of cases 4, 6.

Clinical Features and Diagnosis

• Diagnosis is based on lymph node, bone marrow, or tissue morphology of centrocytic lymphocytes, small cell type, or blastoid variant cells 4.
• The differential diagnosis of MCL includes small lymphocytic lymphoma, marginal zone lymphoma, and follicular lymphoma 4.
• The MCL International Prognostic Index (MIPI) is the prognostic model most often used, incorporating ECOG performance status, age, leukocyte count, and lactic dehydrogenase 4.

Treatment and Management

• Treatment paradigms have evolved along two lines: intensive strategies for younger, fit patients, and non-intensive strategies for older, less fit patients 3.
• Randomized clinical trials have established that bendamustine-rituximab (BR) is more efficacious and less toxic than rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) 3.
• Maintenance rituximab (MR) is beneficial after an R-CHOP induction, and may also be beneficial after a BR induction 3, 5.
• Newer agents, such as Bruton tyrosine kinase inhibitors, have shown promise in the treatment of MCL, particularly in relapsed disease 6, 7.