Primary CNS Lymphoma

Basics to Brilliance: Haematology Podcast

CNS Lymphomas

1% of all NHL
3% of all Brain tumours
Most common subtype (90%) is DLBCL

Clinical division:
1. 1* CNS lymphoma,
2. 2* CNS lymphoma
- TN-SCNSL
- RI-SCNSL
- RC-SCNSL
3. Immune deficiency assoc- HIV; better prog.

Presentation:
- SOL Sx
- Raised ICP: morning headaches w N+V
- Neuropsych, Behavioural, Memory, Language
- Focal motor + Stroke Sx
- Seizures
- Visual Sx and uveitis

Investigations:
- FBC + Blood film (exclude 2* CNS lymphoma and BM), GFR, U&Es
- LDH (prog.)
- Virology (Hep+HIV)
- IGs, SPEp (paraprotein)
- Stereotactic Brain Bx w/ IO rapid cytology and rv of frozen sections
NB: Steroids pre-biopsy ?non-diagnostic results
- LP:
.Leptomeningeal*
.CSF protein- prognostic
.Flow
.Cytospin
.PCR for IGHV r.
- CT Head
- MRI H (w gadolinium) +/- spine

Staging:
-R/O systemic lymphoma
-PET/CT
-US Testes
-Opthalmoscopy/fundoscopy +/- Vitreal biopsy +/- subretinal aspirate
-?BMBx

Pre-treatment:
-Baseline neuropsych + cognitive ax
-Premorbid performance status: ECOG, Echo, GFR, PMHx

Dx w/o Bx
-MRI
-Clinical features
-Clonal B cells in CSF/Vitreous fluid and/or PCR IGHV rearrangement
Treatment:
Induction main:
- MATRIX- younger <70
- MARTA- older >65
Consolidation:
- Whole brain RT
- BCNU Thiotepa AutoSCT- gold standard if fit...Within 6-8 weeks of the 1st day of final induction: consider for all patients with non-progressive disease (EOT MRI)

Trials:
IELSG32 study (Leukemia, 2022)- induction + consolidation choices for < 70
Induction: 3 arms, MTX + Cyt main
- MATRIX- MTX +Cyt + Thiotepa + Ritux -> AutoSCT…..best choice (4 cycles)...7yr 70% survival
Consolidation: efficacy equal AutoSCT and WB-RT, favoured AutoSCT for Sx.
...MATRIX regimen available on NSSG:
- Dose ++ to cross BBB
- Folinic Acid rescue*
- IVF till MTX levels <0.1 umol/L (1st lvl 48hrs after MTX)
- EF >45%
- GFR >50
NB: stop co-trimoxazole, penicillins, aspirin, NSAIDs, PPIs (inhibit MTX clearance)
- MTX build up in 3rd spaces
- Stem cell harvest post #2
- Treatment related mortality 4-7% mostly in #1
- Dose reduce Cytaribin (2/3instead of 4 cycles) if pre-morbid, 25-50% total

MARTA study (Blood, Nov 22): fit for autosct and >65
- 2x MTX, cytarabin and rituximab ->AutoSCT

PRIMAIN study(2017): not fit for autosct >= 65
1. 4x MTX, Ritux + PO procarbazine
2. 6mo of PO procarbazine as maintenance
?WB-RT for residual disease

- Palliative if unfit and older:
Dex
Temozolomide
WB-RT
?IT Chemo in leptomeningeal

IELSG43 study… favoured AutoSCT PFS and OS to de-escalation consol.

Follow Up:
- Response Ax with contrast enhanced MRI scan: 1-2mo after consol.
- Rpt MRI every 3-4mo for 2 years ++-
- CR: MRI NAD, normal eye, clear CSF
- Stable: <50% decrease, <25% increase
- PR: 50% tumor reduction ?persistent CSF
- Progressive: >25% increase and/or new lesions
- Relapse/Refractory
25% asymptomatic
OS 3-5mo
?Trial
Re-Bx and r/o other brain tumors
Restaging
Re-induction w/ salvage chemo
.MATRix if remission > 2 years +/- WB-RT if post auto
.Ifosfamide based: RICE or RIE

Future:
2nd gen BTKis- Ibrutinib or Zanibrutinib