Mamtha Balla: DLBCL – Rapid Board Review Pearls

Mamtha Balla, Transplant Oncology-ID fellow at MD Anderson Cancer Center and Hematology Oncology Fellow at The University of Toledo, shared post on X:

“DLBCL – Rapid Board Review Pearls

(Follow NCCN/ASH/ASCO for latest updates)

Mnemonic: “My MUM taught me the ABCs”

• MUM1+ = ABC (activated B‑cell, worse prognosis)
• CD10+ to GCB (germinal center B‑cell, better)
• CD10– + BCL6+/MUM1– to GCB
• CD10– + MUM1+ to ABC

Frontline Regimens: “Pola Replaces Vince ”

• Standard: R‑CHOP
• High‑risk: Pola‑R‑CHP (Polatuzumab replaces Vincristine)

“8 hits HARD”

• MYC (chr 8) + BCL2/BCL6 to aggressive
• Treat with DA-R-EPOCH + CNS prophylaxis

Big nodes, 10 is good, MUM is bad, 8 hits hard, 100 = Burkitt, early relapse to CAR

Presentation and Workup

• Painless LAD + B-symptoms (fever, drenching sweats, weight loss).
• Examine neck, axilla, groin nodes.
• Labs: CBC, CMP, LDH, Hep B, HIV.
• Imaging: PET/CT for staging (CT neck/chest/abd/pelvis if inpatient).

Diagnosis and Pathology  

• Biopsy gold standard: Excisional (or core) to see architecture.
• FNA = triage only, NOT definitive for lymphoma.
• IHC B‑cell markers: CD19, CD20, CD22, CD79a, PAX5.
• Ki‑67 often high (~80%); Ki‑67 ~100% to think Burkitt until proven otherwise (MYC+).

Cell of Origin (Hans Algorithm)

• GEP: GCB > ABC for prognosis.
• Hans IHC rules:CD10+ to GCB
• CD10– and BCL6+/MUM1– to GCB
• CD10– and (BCL6– or MUM1+) to ABC / non‑GCB  Prognostic, not predictive – doesn’t routinely change frontline choice.

Genetics – “Hits” and Expressors

Chromosomes:

• MYC to chr 8 (“8‑ball”; drives S‑phase).
• BCL2 to chr 18, anti‑apoptotic, t(14;18).
• BCL6 to chr 3, represses MYC/BCL2/p53.
• Double/Triple HIT (FISH – structural)
• Double hit (DH) = MYC + BCL2 and/or BCL6 rearrangements.
• Triple hit (TH) = MYC + BCL2 + BCL6 rearrangements.

Very poor prognosis to DA‑R‑EPOCH + CNS prophylaxis (not R‑CHOP).

Double EXPRESSOR (DE – IHC)

• IHC MYC >40% and BCL2 >50%.
• Worse than standard DLBCL, but less bad than DH/TH.

Many give CNS PPx, but escalation to DA‑EPOCH is controversial.

Ki‑67 Pearl  

• Ki‑67 ≈100% = presume Burkitt to confirm MYC rearrangement, treat with Burkitt-type regimen + CNS PPx.

Staging and Pre‑Treatment  

• Lugano staging (PET‑based)I/II = early (single/bundled nodes on one side of diaphragm).
• III/IV = advanced (nodes both sides ± extranodal, e.g., marrow/liver).

• LDH = key prognostic marker (IPI).
• Hep B serology mandatory before rituximab (reactivation risk).
• Baseline echo before doxorubicin.
• Routine BM biopsy often omitted (PET captures stage; III–IV treated the same).

Frontline Therapy

• Standard risk:R‑CHOP × 6 cycles (± RT for bulky/early localized).
• Intermediate/High risk (IPI ≥2):Pola‑R‑CHP (Polatuzumab‑vedotin + R‑CHP; VINCRISTINE replaced by pola).
• POLARIX: improved PFS vs R‑CHOP.
• Double/Triple hit or PMBL:DA‑R‑EPOCH preferred (etoposide‑based, dose‑adjusted).

EOT PET strategy:

PET‑positive to consider ctDNA MRD (e.g., CLARITY):ctDNA‑negative + low PET uptake to treat like PET‑negative; avoid unnecessary biopsy/escalation.

Relapsed/Refractory DLBCL  

• Early relapse (<12 mo) after R‑CHOP / Pola‑R‑CHP:
• CAR‑T preferred over salvage + ASCT:Axi‑cel or Liso‑cel.

Late relapse (≥12 mo):Salvage chemo (R‑ICE, R‑DHAP, R‑GDP) to ASCT if chemosensitive.

3rd line and beyond (Immunotherapy Era)

• Bispecifics

(BiTEs):Epcoritamab (SC), Glofitamab (IV), Odronextamab (IV).

ADCs:Loncastuximab (anti‑CD19), Pola‑BR (polatuzumab + bendamustine + rituximab).

Toxicity Mnemonic – “C‑N‑R”

• C – CRS (Cytokine Release Syndrome)Seen with CAR‑T and bispecifics: fever, hypotension. Rx: Tocilizumab ± steroids.
• N – Neurotoxicity (ICANS)CAR‑T: confusion, aphasia, seizures. Close neuro checks, treat with steroids.
• R – Reactivation (Rituximab)Hep B reactivation to always check serology and start prophylaxis if positive.

Super High‑Yield One‑Liners  

• DLBCL = core/excisional LN biopsy; FNA alone is inadequate.
• Hans: CD10+ or CD10–/BCL6+/MUM1– = GCB; MUM1+ = ABC.
• Double/triple hit (MYC + BCL2/BCL6 by FISH) to DA‑R‑EPOCH + CNS PPx.
• Double expressor = MYC/BCL2 protein ↑ by IHC; worse, but less than DH.
• Ki‑67 ≈100% = presumptive Burkitt; treat with Burkitt regimen + CNS PPx (not R‑CHOP).
• First‑line: R‑CHOP vs Pola‑R‑CHP in higher‑risk de novo DLBCL.
• Early relapse (<12 mo): CAR‑T > salvage + ASCT.
• 3rd‑line+: bispecifics (epcoritamab, glofitamab, odronextamab), ADCs (loncastuximab, Pola‑BR).
• ctDNA MRD now refines PET‑positive EOT scans.

Thread caption idea:

Diagnostic Innovation: ctDNA / MRD Monitoring

The Update: NCCN Guidelines (v1.2025/2026) now include circulating tumor DNA (ctDNA) as a tool to clarify end-of-treatment PET scans. ( Journal of Clinical Oncology 2025/2026 update)”

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