Primary CNS Lymphoma (PCNSL)
Overview
Primary central nervous system lymphoma, an aggressive extranodal non-Hodgkin lymphoma confined to the brain, spinal cord, leptomeninges, or eye; classified under DLBCL NOS in OncoTree.
Cohorts in the corpus
- pcnsl_msk_2024 — 31 r/r PCNSL patients sequenced on MSK-HemePACT as part of a phase I/II ibrutinib trial at MSK PMID:38995739.
Recurrent alterations
- MYD88 — mutated in 72% of the PCNSL cohort PMID:38995739.
- CD79B — mutated in 48% of the PCNSL cohort PMID:38995739.
- TBL1XR1 — WD40-domain (likely LoF) mutations in 36% of PCNSL cases PMID:38995739.
- CARD11 — mutated in 24% of PCNSL cases PMID:38995739.
- Comprehensive genomic study of 19 immunocompetent PCNSL patients (array-CGH, WES, mate-pair WGS) identified PCNSL-specific biallelic inactivation of TOX (11% HD + 17% monoallelic deletion) and PRKCD; MYD88 L265P mutations in 79%; CDKN2A biallelic loss in 60% (HD 55%); BCR/TLR/NF-κB pathway altered in >90%; 6q21 PRDM1 deletion associated with shorter OS (log-rank P=0.001); dataset: pcnsl_mayo_2015 PMID:25991819
Subtypes
- 21/25 (84%) of profiled PCNSLs in the MSK cohort were non-germinal-center (Hans classifier) PMID:38995739.
Therapeutic landscape
- ibrutinib single-agent 840 mg/day produced 74% ORR (12 CR) in r/r PCNSL; ~10% of patients achieved >3-year durable responses. TBL1XR1 mutation predicted longer PFS (16.5 vs 3.1 months, p=0.0075); MYD88 mutation also associated with longer PFS (9.2 vs 2.9 months); CARD11 coiled-coil mutations marked shorter PFS (2.2 vs 5.5 months) PMID:38995739.
- CSF ctDNA clearance within 4 weeks on ibrutinib correlated with complete and durable response PMID:38995739.
- Prior lines in the cohort included methotrexate (universal), temozolomide, temsirolimus, lenalidomide, and pembrolizumab PMID:38995739.
Sources
This page was processed by crosslinker on 2026-05-14. - PMID:25991819
This page was processed by crosslinker on 2026-05-14.