The field of mantle cell lymphoma (MCL) has witnessed remarkable progress due to relentless advances in molecular pathogenesis, prognostication, and newer treatments. MCL consists of a spectrum of clinical subtypes. Rarely, atypical cyclin D1-negative MCL and in situ MCL neoplasia are identified. Prognostication of MCL is further refined by identifying somatic mutations (such as TP53, NSD2, KMT2D), methylation status, chromatin organization pattern, SOX-11 expression, minimal residual disease (MRD), and genomic clusters. Lymphoid tissue microenvironment studies demonstrated the role of B cell receptor signaling, NFkB, CSF-1, the CD70-SOX-11 axis. Molecular mechanism of resistance, mutation dynamics and pathogenic pathways (BCR, oxidative phosphorylation and MYC) were identified in mediating resistance to various treatments (BTK inhibitors [ibrutinib, acalabrutinib]. Treatment options range from conventional chemoimmunotherapy and stem cell transplantation (SCT) to targeted therapies against BTK (covalent and non-covalent), Bcl2, ROR1, cellular therapy such as anti-CD19 chimeric antigen receptor therapy (CAR-T), and most recently bispecific antibodies against CD19 and CD20. MCL patients frequently relapse. Complex pathogenesis and the management of patients with progression after treatment with BTK/Bcl2 inhibitors and CAR-T (triple-resistant MCL) remains a challenge. Next-generation clinical trials incorporating newer agents and concurrent translational and molecular investigations are ongoing. This article provides a comprehensive update on MCL in 2022. This article is protected by copyright. All rights reserved.
Mantle cell lymphoma in 2022 - A comprehensive update on molecular pathogenesis, risk stratification, clinical approach, and current and novel treatments.