TY - JOUR
T1 - Mantle cell lymphoma
T2 - 2019 update on the diagnosis, pathogenesis, prognostication, and management
AU - Jain, Preetesh
AU - Wang, Michael
N1 - Funding Information:
M.W. has received research funding from Acerta Pharma, Asana Biosciences, BeiGene, Celgene, Janssen, Juno Therapeutics, Kite Pharma, Amgen, Pharmacyclics, AstraZeneca, BioInvent International, Karus, Oncternal, and Novartis; has received honoraria from Janssen, Dava Oncology, OMI, PeerView Institute for Medical Education (PVI); has been a consultant for Acerta Pharma, AstraZeneca, BioInvent International, IO Biotech, Celgene, Juno Therapeutics, Pharmacyclics, MoreHealth, Pulse Biosciences, AxImmune, and Janssen; is on the Board of Directors and advisory committees for Janssen; and received stock or other ownership from MoreHealth. P.J. - none.
Funding Information:
Funding for various MCL studies at MD Anderson Cancer Center was provided in part by the generous philanthropy donated to the MD Anderson Cancer Center B-Cell Lymphoma Moon Shot Program; R21 CA202104 (Michael Wang, PI); and philanthropy funds from The Gary Rogers Foundation and the Fox Family Foundation. Kelley Murfin at
PY - 2019/6
Y1 - 2019/6
N2 - Unprecedented advances in our understanding of the pathobiology, prognostication, and therapeutic options in mantle cell lymphoma (MCL) have taken place in the last few years. Heterogeneity in the clinical course of MCL—indolent vs aggressive—is further delineated by a correlation with the mutational status of the variable region of immunoglobulin heavy chain, methylation status, and SOX-11 expression. Cyclin-D1 negative MCL, in situ MCL neoplasia, and impact of the karyotype on prognosis are distinguished. Apart from Ki-67% and morphology pattern (classic vs blastoid/pleomorphic), the proliferation gene signature has helped to further refine prognostication. Studies focusing on mutational dynamics and clonal evolution on Bruton's tyrosine kinase (BTK) inhibitors (ibrutinib, acalabrutinib) and/or Bcl2 antagonists (venetoclax) have further clarified the prognostic impact of somatic mutations in TP53, BIRC3, CDKN2A, MAP3K14, NOTCH2, NSD2, and SMARCA4 genes. In therapy, long-term follow-up on chemo-immunotherapy studies has demonstrated durable remissions in some patients; however, long-term toxicities, especially from second cancers, are a serious concern with chemotherapy. The therapeutic options in MCL are constantly evolving, with dramatic responses from nonchemotherapeutic agents (ibrutinib, acalabrutinib, and venetoclax). Chimeric antigen receptor therapy and combinations of nonchemotherapeutic agents are actively being studied and our focus is shifting toward making the treatment of MCL chemotherapy-free. Still, MCL remains incurable. The following aspects of MCL continue to pose a challenge: disease transformation, role of the cytokine-microenvironmental milieu, incorporation of positron emission tomography-computerized tomography imaging, minimal residual disease in the prognosis, circulating tumor DNA testing for clonal evolution, predicting resistance to BTK inhibitors, and optimal management of patients who progress on BTK/Bcl2 inhibitors. Next-generation clinical trials should incorporate nonchemotherapeutic agents and personalize the treatment based upon the genomic profile of individual patient. Recent advances in the field of MCL are reviewed.
AB - Unprecedented advances in our understanding of the pathobiology, prognostication, and therapeutic options in mantle cell lymphoma (MCL) have taken place in the last few years. Heterogeneity in the clinical course of MCL—indolent vs aggressive—is further delineated by a correlation with the mutational status of the variable region of immunoglobulin heavy chain, methylation status, and SOX-11 expression. Cyclin-D1 negative MCL, in situ MCL neoplasia, and impact of the karyotype on prognosis are distinguished. Apart from Ki-67% and morphology pattern (classic vs blastoid/pleomorphic), the proliferation gene signature has helped to further refine prognostication. Studies focusing on mutational dynamics and clonal evolution on Bruton's tyrosine kinase (BTK) inhibitors (ibrutinib, acalabrutinib) and/or Bcl2 antagonists (venetoclax) have further clarified the prognostic impact of somatic mutations in TP53, BIRC3, CDKN2A, MAP3K14, NOTCH2, NSD2, and SMARCA4 genes. In therapy, long-term follow-up on chemo-immunotherapy studies has demonstrated durable remissions in some patients; however, long-term toxicities, especially from second cancers, are a serious concern with chemotherapy. The therapeutic options in MCL are constantly evolving, with dramatic responses from nonchemotherapeutic agents (ibrutinib, acalabrutinib, and venetoclax). Chimeric antigen receptor therapy and combinations of nonchemotherapeutic agents are actively being studied and our focus is shifting toward making the treatment of MCL chemotherapy-free. Still, MCL remains incurable. The following aspects of MCL continue to pose a challenge: disease transformation, role of the cytokine-microenvironmental milieu, incorporation of positron emission tomography-computerized tomography imaging, minimal residual disease in the prognosis, circulating tumor DNA testing for clonal evolution, predicting resistance to BTK inhibitors, and optimal management of patients who progress on BTK/Bcl2 inhibitors. Next-generation clinical trials should incorporate nonchemotherapeutic agents and personalize the treatment based upon the genomic profile of individual patient. Recent advances in the field of MCL are reviewed.
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U2 - 10.1002/ajh.25487
DO - 10.1002/ajh.25487
M3 - Article
C2 - 30963600
AN - SCOPUS:85064706200
SN - 0361-8609
VL - 94
SP - 710
EP - 725
JO - American journal of hematology
JF - American journal of hematology
IS - 6
ER -