DLBCL facts Flashcards by Erez Halperin

Immunophenotype of DLBCL

CD20, CD19, CD79a
GCB- CD10 + , Bcl6 +
Non GCB- CD10-, MUM1 +

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IPI DLBCL

LDH
Age 60
ECOG
Advanced stage
> 1 extranodal site

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Sensitivity of Hans criteria in DLBCL

70-80%
Should not determine Tx

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Lymph2Cx assay in DLBCL
LymphoGen

Nano-string gene profiling
Better sensitivity for subclassification for GCB/non GCB

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ctDNA DLBCL

Better in detecting post Tx minimal disease than imaging. not clinically available

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Pts with most benefit from pola in DLBCL

Age> 60
IPI 3-5
ABC

Approved for IPI >= 2

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CART in 1st line DLBCL

R-CHOP lead of 1-2 cycles
High risk pts
ZUMA12 (high IPI, DH or positive interim PET)
ZUMA23 (high risk pts)

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Tafasitamab in 1st line DLBCL

CD19 Ab
Front-MIND
Tafa-len 1st line trial vs RCHOP
Investigational
Result pending

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2nd line CART in DLBCL

Axi-cell (CD28) ZUMA7
OS
Liso-cell (4-1BB)- less toxic TRANSFORM

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CART trials in DLBCL

Axi
ZUMA7- 2nd line
bridging with steroids only
OS advantage
ZUMA1- 3rd line

Liso
TRANSFORM- 2nd line
TRANSCEND- 3rd line

Tisa
BELINDA- 2nd line- negative trial
JULIET- 3rd line

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IgHVH4-34 gene phonotype in DLBCL

ABC
poor prognosis

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Advantage of geriatric assessment in DLBCL

Better identifies pts above/below age 80 as fit/unfit/frail

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X6 RCHOP vs 8X RCHOP in DLBCL

GOYA trial
same effectiveness

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GCSF support in RCHOP

Primary prophylaxis in age > 65
Or comorbities, prior infections, prior cytopenias

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Polatuzumab in 1st line DLBCL

6X Pola-RCHP + 2X R
vs RCHOP
76% vs 70% 2 year PFS
no OS
advantage in ABC, IPI >3, Age>60
higher rates of febrile neutropenia and peripheral neuropathy

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Tafa+ Len Tx in DLBCL

L-MIND
2nd-3rd line
compared to len
60% ORR CR 40%
median PFS 12 months
well tolerated

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Tafasitamab

CD19 Ab

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DA-EPOCH-R OS in PMBCL

Nearly 100% long time OS

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PMBCL subtype

Closer to ABC
MUM1+

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HIV associated DLBCL subtypes

Mild immunodeficiency - GCB/BL
Severe immunodeficiency - ABC

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HIV associated DLBCL Tx

DA-EPOCH-R
But with much lower doses
Specifically for cytoxan
CNS porphylaxis
88% ORR

Testicular, leg type and PCNSL immunophenotype

MYD-88
PDL-1
PIM1
CD79b

Testicular lymphoma Tx

R-CHOP
+
Orchiectomy and contralateral RT
+
CNS prophylaxis

PCNSL workup

Testicular US
Eye exam
BMB
Spinal MRI
PET-CT

Luncastuximab Tesirine in DLBCL 3rd line

CD19 with chemo attached single arm in advanced lines 25% CR PFS 5 months bridginig?

Glofitimab in DLBCL 3rd line

2:1 CD20:CD3 IV 12 cycles Phase II CR 40% mPFS 5 months Obinotuzumab lead in

Epcoritimab in DLBCL 3rd line

1:1 SC until progression CR 40% PFS 5 months

Axi-cell 2nd line in DLBCL

ZUMA7 bridging with steroids only pts rapidly progressing were excluded crossover allowed CR 65%

Tisa-cell 2nd line in DLBCL

BELINDA negative study bridging therapy allowed crossover allowed CR 30% Long time of production

Liso-cell 2nd line in DLBCL

TRANSFORM Salvage allowed CR 66% Sorting of CD4 and CD8 in order to give 1:1 ratio Done in order to reduce toxicity Less toxic

Adriamycin dose adjustments

CKD- no need to dose adjust Liver- reduce to 50% if bili 1-3, 25% if 3-5, don't adminster if >5

Early PTLD definition

12-24 months post transplant

Late PTLD time of occurrence

5-10 post transplant

Risk factors for failure of single agent R in mPTLD

High IPI Bulky disease

Risk factors for failure of single agent R in mPTLD

High IPI Bulky disease

Risk factors for Tx failure in mPTLD

Hypoalbuminemia BM involvement CNS involvement

1st line Tx for PTLD

R x4 Escalation to R CHOP or R EPOCH if signs of high-risk disease If PR but with indolent disease- continue weekly R

Sequential Tx in PTLD

R X4 Followed by CHOP X4

PMBCL immunophenotype

CD19, CD20, CD22, CD79a positive Surface immunoglobulin negative CD30 weak, CD15 negative

Management of Deauville 4 (PR) on end of Tx PETCT in PMBCL

FU or RT Deauville 4 may be a sign of inflammation after DA-EPOCH-R and not of disease

DLBCL survival by IPI

0- 95% 1-2- 80% >2- 55%

Poor genetic risk in DLBCL

MYD88 P53 NOTCH1/2 "MPN"

Important signaling pathway in ABC DLBCL

NFkB

RCHOP-Ibrutinib in 1st line DLBCL

Effective in young pts (<60) And in MCD and N1 genetic phenotypes

Tx of early stage DLBCL

3 R-CHOP + RT 4 R-CHOP

Advantage of DA-EPOCH-R vs RCHOP in PMBCL

No need for RT Better PFS No random comparsion

3rd line Tx in DLBCL

Epco/Glofi Pola-BR Tafa-Len Loncatuximab Selinexor

Pola-BR vs BR in RR DLBCL

OS advantage

CAR-T in 2nd line DLBCL

Phase II PFS and OS advantage

Bispecific in DLBCL

Better ORR and PFS than pola or tafa based regimens

Glofitamab-GemOx in RR DLBCL

vs R-GemOx OS advatage