Mapping Therapeutic Directions in DLBCL: Team Strategies for Prognostic Assessment and Implications for Targeted Therapy and Other Innovative Options

Chair, Krish Patel, MD, prepared useful Practice Aids pertaining to diffuse large B-cell lymphoma for this CME/MOC/NCPD/AAPA/IPCE activity titled “Mapping Therapeutic Directions in DLBCL: Team Strategies for Prognostic Assessment and Implications for Targeted Therapy and Other Innovative Options.” For the full presentation, downloadable Practice Aids, and complete CME/MOC/NCPD/AAPA/IPCE information, and to apply for credit, please visit us at https://bit.ly/4k9jM9d. CME/MOC/NCPD/AAPA/IPCE credit will be available until September 7, 2026.

1. Summary of DLBCL Subtypes and 
Techniques for Prognostic Assessment 
Full abbreviations, accreditation, and disclosure information available at
PeerView.com/DPB40
1. Danilov A et al. The Oncologist. 2022;27:57-66. 2. Alig SF et al. Histopathology. 2025;86:94-105. 3. https://www.cancer.org/cancer/non-hodgkin-lymphoma/detection-diagnosis-staging.html.
4. Stephens DM, Smith SM. Ann Lymph. 2018;2:1-10. 5. Dubois S et al. Clin Cancer Res. 2016;22:2919-2928. 6. Alig SF et al. Histopathology. 2025;86:94-105. ABC
Unclassifed
GCB
MCD
N1
A53
BN2
Cluster 5
Cluster 0
Cluster 2
Cluster 1
Cluster 3EZB
Cluster 4
MYD88, CD798, BCL-12
NOTCH1
TP53
EZH2, MYC, BCL-2, KMT2D
TET2, SGK1
SOCS1, SYK1
ST2
LympGen DLBclass
The Spectrum of DLBCL Subtypes and Importance of COO
1,2
Selected Principles and Tools for Diagnosis of DLBCL
3-6
For Biopsy of Lymph Node
Fine needle aspiration (FNA) is inadequate
Excisional or incisional biopsy is optimal
Often diagnosis made from core biopsy (multiple cores ideal)
Multiple Diagnostic Tools
Immunohistochemistry (IHC)
Flow cytometry
Molecular analysis to detect Ig gene rearrangements
Karyotype or FISH for major translocations
Next-generation sequencing (NGS) (also for ctDNA MRD assessment)
BCL-6, NOTCH2
Sample Genetic
Determinants
Genetic SubtypeCOO

2. Resources for Prognostic Evaluation of DLBCL 
Full abbreviations, accreditation, and disclosure information available at PeerView.com/DPB40
a
 Data in patients who received an R-CHOP-based regimen. 
1. Sehn LH et al. Blood. 2007;109:1857-1861. 2. Zhou Z et al. Blood. 2014;123:837-842. 3. Ruppert AS et al. Blood. 2020;135:2041-2048. 4. Mahadevia H et al. Lymphatics. 2024;2:10-24. 5. Maurer MJ et al.≤Haematologica. 2023;108:2874-2879. 6. Devi K et al.≤Leuk Res Rep. 2021;16:100284. 
7. Lenz G et al.≤N≤Engl≤J Med.≤2008;359:2313-2323. R-IPI and NCCN-IPI Are Tools for Predicting Outcomes in Untreated Aggressive B-Cell Lymphoma
1-4
Triple-hit≤
MYC + BCL2 + BCL6
ABC/non-GCB
Double-hit≤
MYC + BCL2
5-y OS by Risk Group, %
a
Risk ScorePrognostic Factors
R-IPI
92.5
81.3
60.9
Very good (0 prognostic factors)
Good (1-2 prognostic factors)
Poor (3-5 prognostic factors)
Age >60 y
LDH > ULN
Disease stage III or IV
ECOG PS >1
Extranodal sites of disease >1
NCCN-IPI
Age, y
  >40 to ≤60 (score = 1)
  >60 to ≤75 (score = 2)
  >75 (score = 3)
Normalized LDH
  >1 to ≤3 (score = 1)
  >3 (score = 2)
Ann Arbor Stage III-IV (score = 1)
Extranodal disease (score = 1)
ECOG PS ≥2 (score = 1)
92.1
83.9
62.7
49
Low (0-1 points)
Low-intermediate (2-3 points)
High-intermediate (4-5 points)
High (≥6 points)
Disease Biology and
Subtype Have 
Implications for 
Treatment With CIT
5-7
Access NCCN guidelines
with NCCN-IPI here
Access R-IPI 
online calculator here
2-y OS of ~20% to 30%
with standard therapy
5-y OS of ~30% to 40% 
with R-CHOP
3-y OS of ~30% to 40%
with R-CHOP