ctDNA and Metabolites in CSF as Early Biomarkers of Secondary CNS Involvement in Diffuse Large B-cell Lymphoma

Pilot Study:

Inclusion criteria:

1. Verified or suspected primary CNS lymphoma or verified or suspected DLBCL relapsed in the CNS
2. Treatment of the relapse not initiated (except pretreatment with corticosteroids)
3. Age ≥ 18 years
4. Patient must consent to genetic and metabolomic analysis of their cancer
5. Written informed consent

Exclusion criteria:

1. Evidence of a CNS mass creating mass-effect or midline shift such that lumbar puncture is contraindicated
2. Other contraindications to lumbar puncture according to local guidelines
3. Other previous or current hematological malignancy
4. Prior treatment for CNS disease (except CNS prophylaxis in first line lymphoma treatment)
5. Known CNS autoimmune or inflammatory disease
6. Known HIV infection
7. Patient is currently receiving treatment for DLBCL

Study 1

Inclusion criteria:

1. Previously diagnosed histologically documented DLBCL
2. Verified relapsed DLBCL
3. ≥ 1 prior DLBCL treatments
4. Treatment of the relapse not initiated (except pretreatment with corticosteroids)
5. Being able to undergo standard assessment ( eg, Fluorine-18 fluorodeoxyglucose positron emission tomography (18F-FDG-PET), MRI of the neuroaxis and bone marrow biopsy)
6. Tumor biopsy and/or bone-marrow biopsy used for diagnosis available
7. Age ≥ 18 years
8. ECOG performance status of 0, 1 or 2
9. Life expectancy ≥ 12 weeks
10. Patient must consent to permit genetic and metabolomic analysis of their cancer
11. Patient must consent to permit access to records in order to ascertain progression or relapse of their cancer
12. Written informed consent

Exclusion criteria:

1. Evidence of a CNS mass creating mass-effect or midline shift such that lumbar puncture is contraindicated
2. Other contraindications to lumbar puncture according to local guidelines
3. Other previous or current hematological malignancy
4. Previous or current primary CNS malignancy including know DLBCL relapse to the CNS
5. Prior treatment for CNS disease (except CNS prophylaxis in first line lymphoma treatment)
6. Known CNS autoimmune or inflammatory disease
7. Known HIV infection
8. Patient is currently receiving treatment for DLBCL (except pretreatment with corticosteroids)

Study 2

Inclusion criteria:

1. A newly diagnosed and histologically verified DLBCL
2. No prior DLBCL treatments
3. Anti-lymphoma treatment not initiated (except pretreatment with corticosteroids)
4. CNS-IPI \>/= 3
5. Being able to undergo standard assessment ( eg, Fluorine-18 fluorodeoxyglucose positron emission tomography (18F-FDG-PET), MRI of the neuroaxis and bone marrow biopsy)
6. Tumor biopsy and/or bone-marrow biopsy used for diagnosis available
7. Age ≥ 18 years
8. ECOG performance status of 0, 1 or 2
9. Life expectancy \>/= 12 weeks
10. Patient must consent to permit genetic analysis of their cancer
11. Patient must consent to permit access to records in order to ascertain progression or relapse of their cancer
12. Written informed consent

Exclusion criteria:

1. Evidence of a CNS mass creating mass-effect or midline shift such that lumbar puncture is contraindicated
2. Other contraindications to lumbar puncture according to local guidelines
3. Other previous or current hematological malignancy
4. Previous or current primary CNS malignancy including primary CNS lymphoma
5. Prior treatment for CNS disease
6. Known CNS autoimmune or inflammatory disease
7. Known HIV infection
8. Patient is currently receiving treatment for DLBCL (except pretreatment with corticosteroids)