RT Book, Section
A1 Jain, Preetesh
A1 Wang, Michael
A2 Kantarjian, Hagop M.
A2 Wolff, Robert A.
A2 Rieber, Alyssa G.
SR Print(0)
ID 1190833123
T1 Mantle Cell Lymphoma
T2 The MD Anderson Manual of Medical Oncology, 4e
YR 2022
FD 2022
PB McGraw Hill Education
PP New York, NY
SN 9781260467642
LK accessmedicine.mhmedical.com/content.aspx?aid=1190833123
RD 2024/04/16
AB KEY  CONCEPTSAdvances  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.