++
KEY CONCEPTS
Advances in the field of mantle cell lymphoma (MCL) have significantly changed our understanding of its pathobiology. With the treatment modalities currently available, the response rates and survival have improved but this lymphoma still remains incurable. Heterogeneity in clinical presentation of patients poses a therapeutic dilemma among the clinicians. Broadly, two distinct clinical variants are recognized—an indolent non-nodal leukemic phase, which is generally SOX-11–negative, and another nodal or extranodal SOX-11–positive conventional MCL.
Pathogenic relevance of factors such as overexpression of SOX-11 in lymphoma cells, proliferative lymph node microenvironment, clonal and subclonal evolution, presence of mutations in epigenetic modifiers, and presence of CCND1 genes in addition to other cell cycle–associated genetic aberrancies are closely associated with survival, growth, proliferation and maintenance of MCL clones in tumor microenvironment and maintain minimal residual disease.
An improved understanding of B-cell receptor kinase signaling pathways, such as Bruton tyrosine kinase (BTK) pathway is identified as a critical pathway for therapeutic targeting of MCL B-cells.
Patients with MCL who exhibit high-risk features at initial diagnosis such as high-risk MCL international prognostic index (MIPI) score, blastoid and/or pleomorphic histology, high Ki-67% (≥50%), TP53 aberrations, MYC gene rearrangement, complex genomics (CCND1, CDKN2A, NSD2, KMT2D, SMARCA4, and NOTCH1 or NOTCH2 mutations) and complex karyotype generally portend a poor prognosis and frequent relapses.
Long-term follow-up of intensive chemoimmunotherapy studies demonstrated durable responses and remissions in a subset of patients with MCL. However, the advent of newer agents for frontline therapy, such as ibrutinib, acalabrutinib, and their combinations with rituximab and venetoclax, are very promising and under active investigation.
The focus of treating MCL is rapidly changing toward investigation of “chemotherapy-free” agents such as BTK inhibitors, venetoclax, and rituximab. Most recently, the FDA approval of anti–CD19-chimeric antigen receptor therapy (CAR-T)—brexucabtagene autoleucel—has been a landmark advancement in treating patients with MCL.
++
Mantle cell lymphoma (MCL) is a distinct category of B-cell non-Hodgkin lymphoma (B-NHL). These patients generally exhibit an aggressive, albeit heterogeneous, clinical course but smoldering or indolent forms of MCL are also recognized. In this chapter, we will provide a comprehensive update on various aspects of MCL—factors associated with the etiopathogenesis, clinical and diagnostic features, advances in risk stratification, management of MCL, current challenges, and management approach at MDACC to treat MCL.
+++
INCIDENCE AND POSSIBLE PREDISPOSING RISK FACTORS
++
MCL comprises about 3% to 10% of adult-onset NHL in Western countries, with an incidence of approximately four to eight cases per million persons per year, and its incidence is rising, with an estimated 3320 cases1 diagnosed in 2016.2–4 Its incidence appears to be rising in older adult patients (age ≥65 years) and in non-Hispanic whites.5 The median age at initial presentation in Western countries is 68 or 71 years old. Furthermore, the incidence of MCL in Asian countries is variable6,7 (1%–6%) and appears to be lower than in Western countries, and MCL ...