Basics
This is the most common subtype of nHL, accounting for ~40% of all cases
Diffuse Large B-Cell Lymphoma
The ABC subtype of DLBCL is characterized by chronic B cell receptor signaling and constitutive activation of this transcription factor complex (remember it's a ___ addict)
NF-kB (nuclear factor kappa light chain enhancer of activated B cells for long)
This clinical prognostic scoring system for DLBCL incorporates age, LDH, performance status, stage and number of extranodal sites
International prognostic index (IPI)
This 5-drug chemoimmunotherapy regimen — given every 21 days for 6 cycles — has been the standard of care for advanced-stage DLBCL for over two decades.
R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone)?
For fit patients with DLBCL that relapses within 12 months or is primary refractory, this CD19-directed cellular therapy has emerged as the preferred second-line option over salvage chemotherapy plus autologous transplant
CAR T-cell therapy
These are the two molecular subtypes of DLBCL, defined by gene expression profiling based on cell of origin (COO)
Germinal center B-cell like (GCB) and activated B-cell like (ABC)
What gene is the master key to driving aberrant cell proliferation in the dark zone and characteristically expressed in GCB subtype of DLBCL?
BCL6
**Patients with DLBCL who do not relapse within this time frame after treatment have survival comparable to the general population
24 months
Rituximab targets this cell surface antigen expressed on B cells.
CD20
Epcoritamab and glofitamab are examples of this class of immunotherapy, approved for relapsed/refractory DLBCL after ≥2 prior lines, that simultaneously engage T cells and a tumor antigen.
bispecific antibodies (CD3×CD20 bispecific antibodies)
This IHC-based algorithm uses CD10, BCL6 and MUM1 expression to classify DLBCL into GCB and non-GCB subtypes
Hans algorithm (Hans classifier)
a DLBCL harboring concurrent rearrangements of MYC and BCL2 is classified by the WHO as this entity
Double hit DLBCL (high grade B-cell lymphoma)
This initial lab value carries some prognostic indication in a newly diagnosed DLBCL
LDH
In the POLARIX trial, this antibody-drug conjugate replaced vincristine in R-CHOP and demonstrated improved 2-year PFS, particularly in patients with IPI ≥2.
polatuzumab vedotin
**Tafasitamab is approved in combination with this immunomodulatory agent for relapsed/refractory DLBCL in patients not eligible for autologous stem cell transplant.
lenalidomide
This is the preferred biopsy method for diagnosing DLBCL, as fine needle aspiration is considered inadequate
excisional biopsy
This genetic subtype of DLBCL, identified by Schmitz et al., is defined by the co-occurrence of MYD88 L265P and CD79B mutations and carries a poor prognosis
MCD subtype
This IPI risk model uses 6 factors — including kidney or adrenal involvement — to stratify DLBCL patients into low, intermediate, and high risk for CNS relapse.
CNS-IPI (Prognostic Model to Assess the Risk of CNS Disease)
**In the FLYER trial, patients with limited-stage, non-bulky, low-risk DLBCL achieved equivalent outcomes with only this many cycles of R-CHOP (plus 2 additional cycles of rituximab alone).
4 cycles
For patients with late relapse (>12 months) who are transplant-eligible, the standard approach is salvage chemotherapy followed by this consolidative procedure
autologous stem cell transplantation
Of the two cell of origin (COO) types, this one carries and inferior prognosis, with a 3 year PFS of 40-50%
Unlike double-hit lymphomas (which have gene rearrangements), these lymphomas overexpress MYC and BCL2 without translocations
Double-expresser lymphomas
Mutations in this tumor suppressor gene, particularly in the DNA-binding domain, are associated with poor prognosis in DLBCL and are frequent in double-hit lymphomas.
TP53
For patients with concurrent MYC and BCL2 rearrangements (double-hit lymphoma), this dose-adjusted infusional regimen is commonly used instead of standard R-CHOP
DA-EPOCH-R (dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab)
This first-in-class selective inhibitor of nuclear export (XPO1 inhibitor) received accelerated FDA approval for relapsed/refractory DLBCL after ≥2 prior lines of therapy.
selinexor (Xpovio)