Secondary CNS Lymphoma

Synchronous CNS and systemic lymphoma at initial presentation (treatment-naïve; TN-SCNSL)
- CNS relapse without recurrent systemic lymphoma (relapsed isolated CNS lymphoma; RI-SCNSL)
- Relapsed concomitant systemic and CNS disease following treatment for systemic lymphoma (RC-SCNSL)

Generally hybrid disease

Investigations
- MRI Head w gadolinium
- PET-CT
- Testicular US (blood testes barrier influences treatment)
- Opthalmoscopy/fundoscopy +/- Vitreal biopsy +/- subretinal aspirate – could need RT
- Lymph node Biopsy
NB: Worthwhile to remember patient hx re relapses
- ?Stereotactic Brain Biopsy w/ Intraoperative rapid cytology and rv of frozen sections......NB: Steroids pre-biopsy may yield non-diagnostic results (1/3 if 7 days steroids)
- Correlate with imaging and timescale
- LP
o Good for leptomeningeal (15%) which can be missed on MRI
o CSF protein levels are prognostic
o Flow cytometry
o Cytospin
o PCR for IGHV rearrangement: sens.

Trial: MARIETTA study, or also known as the IE LSG 42
- Single arm prospective trial, 75 patients
- +/- Steroid pre-phase –>MATRIX + RICE alternating induction x3–>CR/PR ->Carmustine-Thiotepa AutoSCT
- Pre-morbid performance status <=3
- 2-year overall survival for all of those patients included in the trial just under 50%
- NB: cytaribin omissions if poor performance status
- RICE (Ritux isophosphamide, carboplatin and etoposide)...NB, peripheral neuropathy and neurotoxicitiy
- TN-SCNSL best 70% 2 year PFS
- RI-SCNSL 40% 2 year PFS... can also be given just MATRIX
- RC-SCNSL 14% 2 year PFS
- NB if frail elderly, change MATRIX to MARTA
Response assessment :
- TN-SCNSL and RC-SCNSL
o Brain MRI +/- Spine every 2 cycles
o PET scan every 2-3 cycles
o PET and MRI pre-auto, determine least partial response
o End of treatment PET (6-8 weeks post) and MRI

RI-SCNSL : MRI brain +/- spine every 2 cycles...PET only if suspicion of progression elsewhere

Relapse post MARIETTA :

-BTKi ?compassionate access vs Trial
-ZUMA7 trial: CAR-T (anti CD19) NB : ICANS/CRS....Approved for DLBCL 12 relapse within 12 months and primary refractory disease that hasn’t responded
- PALLIATIVE CARE

NB Immuno-privileged sites :

- Primary Intraocular Lymphoma :
o Stage w PET, MRI head, US Testes
o MATRIX vs MARTA vs PREMAINE as frailty allows (like 1’ CNS) –> AutoSCT
o +/- Occular RT
o Frail++ +-> Intravitreal MTX
- Primary Testicular Lymphoma
o If 1 testicle involved 1/3 of patients have the other involved too
o US Testes –> Orchidectomy + histopathology...if lymphoma ->imaging and investigations as above
o LP with above investigations as 1/3 have CNS involvement
o ?skin lesions sometimes in testicular lymphoma
o RCHOP vs RPolaChP + CNS prophylaxis w MTX
o Radiotherapy (30gy) to contralateral testes to reduce contralateral Relapse risk and/or BL orchidectomy- fertility discussion
o Systemic chemotherapy because of microspread to nodes